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Recent Articles in BMC Neuroscience

Visalli V, Muscoli C, Sacco I, Sculco F, Palma E, Costa N, Colica C, Rotiroti D, Mollace V
N-acetylcysteine prevents HIV gp 120-related damage of human cultured astrocytes: correlation with glutamine synthase dysfunction.
BMC Neurosci. 2007 Dec 6;8(1):106.
ABSTRACT: BACKGROUND: HIV envelope gp 120 glycoprotein is released during active HIV infection of brain macrophages thereby generating inflammation and oxidative stress which contribute to the development of the AIDS-Dementia Complex (ADC). Gp120 has also been found capable to generate excitotoxic effect on brain tissue via enhancement of glutamatergic neurotransmission, leading to neuronal and astroglial damage, though the mechanism is still to be better understood. Here we investigated on the effect of N-acetylcysteine (NAC), on gp120-induced damage in human cultured astroglial cells and the possible contribution of gp120-related reacting oxygen species (ROS) in the imbalanced activity of glutamine synthase (GS), the enzyme that metabolizes glutamate into glutamine within astroglial cells playing a neuroprotective role in brain disorders. RESULTS: Incubation of Lipari human cultured astroglial cells with gp 120 (0.1-10 nM) produced a significant reduction of astroglial cell viability and apoptosis as evaluated by TUNEL reaction and flow cytometric analysis (FACS). This effect was accompanied by lipid peroxidation as detected by means of malondialdehyde assay (MDA). In addition, gp 120 reduced both glutamine concentration in astroglial cell supernatants and GS expression as detected by immunocytochemistry and western blotting analysis. Pre-treatment of cells with NAC (0.5-5 mM), dose-dependently antagonised astroglial apoptotic cell death induced by gp 120, an effect accompanied by significant attenuation of MDA accumulation. Furthermore, both effects were closely associated with a significant recovery of glutamine levels in cell supernatants and by GS expression, thus suggesting that overproduction of free radicals might contribute in gp 120-related dysfunction of GS in astroglial cells. CONCLUSIONS: In conclusion, the present experiments demonstrate that gp 120 is toxic to astroglial cells, an effect accompanied by lipid peroxidation and by altered glutamine release. All the effects of gp120 on astroglial cells were counteracted by NAC thus suggesting a novel and potentially useful approach in the treatment of glutammatergic disorders found in HAD patients. [Abstract/Link to Full Text]

Schneider M, Spanagel R, Zhang SJ, Bading H, Klugmann M
Adeno-associated virus (AAV)-mediated suppression of Ca2+/calmodulin kinase IV activity in the nucleus accumbens modulates emotional behaviour in mice.
BMC Neurosci. 2007 Dec 3;8(1):105.
ABSTRACT: BACKGROUND: Calcium/calmodulin-dependent protein kinase IV (CaMKIV) controls activity-dependent gene transcription by regulating the activity of the cyclic AMP response element binding protein (CREB). This signaling pathway is involved in gating emotional responses in the CNS but previous studies did not address the potential roles of CaMKIV in discrete brain regions. In the present study, we aimed at specifically dissecting the role of CaMKIV in the nucleus accumbens of adult mice. RESULTS: We used recombinant adeno-associated virus (rAAV)-mediated gene transfer of a dominant-negative CaMKIV variant (rAAV-dnCaMKIV) to inhibit endogenous CaMKIV in the nucleus accumbens. rAAV-dnCaMKIV treated animals were subjected to a battery of tests including, prepulse inhibition of the acoustic startle response, open field, social interaction and anxiety-related behaviour. We found that basal locomotor activity in the open field, and prepulse inhibition or startle performance were unaltered in mice infected with rAAV-dnCaMKIV in the nucleus accumbens. However, anxiogenic effects were revealed in social interaction testing and the light/dark emergence test. CONCLUSIONS: Our findings suggest a modulatory role of CaMKIV in the nucleus accumbens in anxiety-like behaviour but not sensorimotor gating. [Abstract/Link to Full Text]

Wautier F, Wislet-Gendebien S, Chanas G, Rogister B, Leprince P
Regulation of nestin expression by thrombin and cell density in cultures of bone mesenchymal stem cells and radial glial cells.
BMC Neurosci. 2007 Nov 30;8(1):104.
ABSTRACT: BACKGROUND: Bone marrow stromal cells and radial glia are two stem cell types with neural phenotypic plasticity. Bone marrow mesenchymal stem cells can differentiate into osteocytes, chondrocytes and adipocytes, but can also differentiate into non-mesenchymal cell, i.e. neural cells in appropriate in vivo and in vitro experimental conditions. Likewise, radial glial cells are the progenitors of many neurons in the developing cortex, but can also generate astrocytes. Both cell types express nestin, an intermediate filament protein which is the hallmark of neural precursors. RESULTS: In this study, we demonstrate that thrombin, a multifunctional serine protease, stimulates the growth of radial glial cells (RG) and mesenchymal stem cells (MSCs) in a dose-dependent manner. In RG, the mitogenic effect of thrombin is correlated with increased expression of nestin but in MSCs, this mitogenic effect is associated with nestin down-regulation. Both cell types express the PAR-1 type receptor for Thrombin and the effect of Thrombin on both cell types can be mimicked by its analogue TRAP-6 activating specifically this receptor subtype or by serum which contains various amount of thrombin. Moreover, we also demonstrate that serum deprivation-induced expression of nestin in MSCs is inhibited by high cell density (> 50,000 cells/cm2). CONCLUSIONS: This work shows that thrombin stimulates the growth of both RG and MSCs and that nestin expression by MSCs and RG is regulated in opposite manner by thrombin in vitro. Thrombin effect is thus associated in both cell types with a proliferating, undifferentiated state but in RG this involves the induction of nestin expression, a marker of immaturity for neural progenitors. In MSCs however, nestin expression, as it corresponds to a progression from the mesenchymal "undifferentiated", proliferating phenotype toward acquisition of a neural fate, is inhibited by the mitogenic signal. [Abstract/Link to Full Text]

Ubeda-Banon I, Novejarque A, Mohedano-Moriano A, Pro-Sistiaga P, de la Rosa-Prieto C, Insausti R, Martinez-Garcia F, Lanuza E, Martinez-Marcos A
Projections from the posterolateral olfactory amygdala to the ventral striatum: neural basis for reinforcing properties of chemical stimuli.
BMC Neurosci. 2007 Nov 29;8(1):103.
ABSTRACT: BACKGROUND: Vertebrates sense chemical stimuli through the olfactory receptor neurons whose axons project to the main olfactory bulb. The main projections of the olfactory bulb are directed to the olfactory cortex and olfactory amygdala (the anterior and posterolateral cortical amygdalae). The posterolateral cortical amygdaloid nucleus mainly projects to other amygdaloid nuclei; other seemingly minor outputs are directed to the ventral striatum, in particular to the olfactory tubercle and the islands of Calleja. RESULTS: Although the olfactory projections have been previously described in the literature, injection of dextran-amines into the rat main olfactory bulb was performed with the aim of delimiting the olfactory tubercle and posterolateral cortical amygdaloid nucleus in our own material. Injection of dextran-amines into the posterolateral cortical amygdaloid nucleus of rats resulted in anterograde labeling in the ventral striatum, in particular in the core of the nucleus accumbens, and in the medial olfactory tubercle including some islands of Calleja and the cell bridges across the ventral pallidum. Injections of Fluoro-Gold into the ventral striatum were performed to allow retrograde confirmation of these projections. CONCLUSIONS: The present results extend previous descriptions of the posterolateral cortical amygdaloid nucleus efferent projections, which are mainly directed to the core of the nucleus accumbens and the medial olfactory tubercle. Our data indicate that the projection to the core of the nucleus accumbens arises from layer III; the projection to the olfactory tubercle arises from layer II and is much more robust than previously thought. This latter projection is directed to the medial olfactory tubercle including the corresponding islands of Calleja, an area recently described as critical node for the neural circuit of addiction to some stimulant drugs of abuse. [Abstract/Link to Full Text]

Biskup S, Moore DJ, Rea A, Lorenz-Deperieux B, Coombes CE, Dawson VL, Dawson TM, West AB
Dynamic and redundant regulation of LRRK2 and LRRK1 expression.
BMC Neurosci. 2007 Nov 28;8(1):102.
ABSTRACT: BACKGROUND: Mutations within the leucine-rich repeat kinase 2 (LRRK2) gene account for a significant proportion of autosomal-dominant and some late-onset sporadic Parkinson's disease. Elucidation of LRRK2 protein function in health and disease provides an opportunity for deciphering molecular pathways important in neurodegeneration. In mammals, LRRK1 and LRRK2 protein comprise a unique family encoding a GTPase domain that controls intrinsic kinase activity. The expression profiles of the murine LRRK proteins have not been fully described and insufficiently characterized antibodies have produced conflicting results in the literature. RESULTS: Herein, we comprehensively evaluate twenty-one commercially available antibodies to the LRRK2 protein using mouse LRRK2 and human LRRK2 expression vectors, wild-type and LRRK2-null mouse brain lysates and human brain lysates. Eleven antibodies detect over-expressed human LRRK2 while four antibodies detect endogenous human LRRK2. In contrast, two antibodies recognize over-expressed mouse LRRK2 and one antibody detected endogenous mouse LRRK2. LRRK2 protein resides in both soluble and detergent soluble protein fractions. LRRK2 and the related LRRK1 genes encode low levels of expressed mRNA species corresponding to low levels of protein both during development and in adulthood with largely redundant expression profiles. CONCLUSIONS: Despite previously published results, commercially available antibodies generally fail to recognize endogenous mouse LRRK2 protein; however, several antibodies retain the ability to detect over-expressed mouse LRRK2 protein. Over half of the commercially available antibodies tested detect over-expressed human LRRK2 protein and some have sufficient specificity to detect endogenous LRRK2 in human brain. The mammalian LRRK proteins are developmentally regulated in several tissues and coordinated expression suggest possible redundancy in the function between LRRK1 and LRRK2. [Abstract/Link to Full Text]

Andrykiewicz A, Patino L, Naranjo JR, Witte M, Hepp-Reymond MC, Kristeva R
Corticomuscular synchronization with small and large dynamic force output.
BMC Neurosci. 2007 Nov 27;8(1):101.
ABSTRACT: BACKGROUND: Over the last years much research has been devoted to investigating the synchronization between cortical motor and muscular activity as measured by EEG/MEG-EMG coherence. The main focus so far has been on corticomuscular coherence (CMC) during static force condition, for which coherence in beta-range has been described. In contrast, we showed in a recent study [1] that dynamic force condition is accompanied by gamma-range CMC. The modulation of the CMC by various dynamic force amplitudes, however, remained uninvestigated. The present study addresses this question. We examined eight healthy human subjects. EEG and surface EMG were recorded simultaneously. The visuomotor task consisted in isometric compensation for 3 forces (static, small and large dynamic) generated by a manipulandum. The CMC, the cortical EEG spectral power (SP), the EMG SP and the errors in motor performance (as the difference between target and exerted force) were analyzed. RESULTS: For the static force condition we found the well-documented, significant beta-range CMC (15-30Hz) over the contralateral sensorimotor cortex. Gamma-band CMC (30-45Hz) occurred in both small and large dynamic force conditions without any significant difference between both conditions. Although in some subjects beta-range CMC was observed during both dynamic force conditions no significant difference between conditions could be detected. With respect to the motor performance, the lowest errors were obtained in the static force condition and the highest ones in the dynamic condition with large amplitude. However, when we normalized the magnitude of the errors to the amplitude of the applied force (relative errors) no significant difference between both dynamic conditions was observed. CONCLUSIONS: These findings confirm that during dynamic force output the corticomuscular network oscillates at gamma frequencies. Moreover, we show that amplitude modulation of dynamic force has no effect on the gamma CMC in the low force range investigated. We suggest that gamma CMC is rather associated with the internal state of the sensorimotor system as supported by the unchanged relative error between both dynamic conditions. [Abstract/Link to Full Text]

Szpara ML, Vranizan K, Tai YC, Goodman CS, Speed TP, Ngai J
Analysis of gene expression during neurite outgrowth and regeneration.
BMC Neurosci. 2007 Nov 23;8(1):100.
ABSTRACT: BACKGROUND: The ability of a neuron to regenerate functional connections after injury is influenced by both its intrinsic state and also by extrinsic cues in its surroundings. Investigations of the transcriptional changes undergone by neurons during in vivo models of injury and regeneration have revealed many transcripts associated with these processes. Because of the complex milieu of interactions in vivo, these results include not only expression changes directly related to regenerative outgrowth and but also unrelated responses to surrounding cells and signals. In vitro models of neurite outgrowth provide a means to study the intrinsic transcriptional patterns of neurite outgrowth in the absence of extensive extrinsic cues from nearby cells and tissues. RESULTS: We have undertaken a genome-wide study of transcriptional activity in embryonic superior cervical ganglia (SCG) and dorsal root ganglia (DRG) during a time course of neurite outgrowth in vitro. Gene expression observed in these models likely includes both developmental gene expression patterns and regenerative responses to axotomy, which occurs as the result of tissue dissection. Comparison across both models revealed many genes with similar gene expression patterns during neurite outgrowth. These patterns were minimally affected by exposure to the potent inhibitory cue Semaphorin3A, indicating that this extrinsic cue does not exert major effects at the level of nuclear transcription. We also compared our data to several published studies of DRG and SCG gene expression in animal models of regeneration, and found the expression of a large number of genes in common between neurite outgrowth in vitro and regeneration in vivo. CONCLUSIONS: Many gene expression changes undergone by SCG and DRG during in vitro outgrowth are shared between these two tissue types and in common with in vivo regeneration models. This suggests that the genes identified in this in vitro study may represent new candidates worthy of further study for potential roles in the therapeutic regrowth of neuronal connections. [Abstract/Link to Full Text]

Wilson R, Bate C, Boshuizen R, Williams A, Brewer J
Squalestatin alters the intracellular trafficking of a neurotoxic prion peptide.
BMC Neurosci. 2007;899.
ABSTRACT: BACKGROUND: Neurotoxic peptides derived from the protease-resistant core of the prion protein are used to model the pathogenesis of prion diseases. The current study characterised the ingestion, internalization and intracellular trafficking of a neurotoxic peptide containing amino acids 105-132 of the murine prion protein (MoPrP105-132) in neuroblastoma cells and primary cortical neurons. RESULTS: Fluorescence microscopy and cell fractionation techniques showed that MoPrP105-132 co-localised with lipid raft markers (cholera toxin and caveolin-1) and trafficked intracellularly within lipid rafts. This trafficking followed a non-classical endosomal pathway delivering peptide to the Golgi and ER, avoiding classical endosomal trafficking via early endosomes to lysosomes. Fluorescence resonance energy transfer analysis demonstrated close interactions of MoPrP105-132 with cytoplasmic phospholipase A2 (cPLA2) and cyclo-oxygenase-1 (COX-1), enzymes implicated in the neurotoxicity of prions. Treatment with squalestatin reduced neuronal cholesterol levels and caused the redistribution of MoPrP105-132 out of lipid rafts. In squalestatin-treated cells, MoPrP105-132 was rerouted away from the Golgi/ER into degradative lysosomes. Squalestatin treatment also reduced the association between MoPrP105-132 and cPLA2/COX-1. CONCLUSION: As the observed shift in peptide trafficking was accompanied by increased cell survival these studies suggest that the neurotoxicity of this PrP peptide is dependent on trafficking to specific organelles where it activates specific signal transduction pathways. [Abstract/Link to Full Text]

Porterfield VM, Piontkivska H, Mintz EM
Identification of novel light-induced genes in the suprachiasmatic nucleus.
BMC Neurosci. 2007 Nov 19;8(1):98.
ABSTRACT: BACKGROUND: The transmission of information about the photic environment to the circadian clock involves a complex array of neurotransmitters, receptors, and second messenger systems. Exposure of an animal to light during the subjective night initiates rapid transcription of a number of immediate-early genes in the suprachiasmatic nucleus of the hypothalamus. Some of these genes have known roles in entraining the circadian clock, while others have unknown functions. Using laser capture microscopy, microarray analysis, and quantitative real-time PCR, we performed a comprehensive screen for changes in gene expression immediately following a 30 minute light pulse in suprachiasmatic nucleus of mice. RESULTS: The results of the microarray screen successfully identified previously known light-induced genes as well as several novel genes that may be important in the circadian clock. Newly identified light-induced genes include early growth response 2, proviral integration site 3, growth-arrest and DNA-damage-inducible 45 beta, and TCDD-inducible poly(ADP-ribose) polymerase. Comparative analysis of promoter sequences revealed the presence of evolutionarily conserved CRE and associated TATA box elements in most of the light-induced genes, while other core clock genes generally lack this combination of promoter elements. CONCLUSIONS: The photic signalling cascade in the suprachiasmatic nucleus activates an array of immediate-early genes, most of which have unknown functions in the circadian clock. Detected evolutionary conservation of CRE and TATA box elements in promoters of light-induced genes suggest that the functional role of these elements has likely remained the same over evolutionary time across mammalian orders. [Abstract/Link to Full Text]

Bourane S, Mechaly I, Venteo S, Garces A, Fichard A, Valmier J, Carroll P
A SAGE-based screen for genes expressed in sub-populations of neurons in the mouse dorsal root ganglion.
BMC Neurosci. 2007 Nov 19;8(1):97.
ABSTRACT: BACKGROUND: The different sensory modalities temperature, pain, touch and muscle proprioception are carried by somatosensory neurons of the dorsal root ganglia. Study of this system is hampered by the lack of molecular markers for many of these neuronal sub-types. In order to detect genes expressed in sub-populations of somatosensory neurons, gene profiling was carried out on wild-type and TrkA mutant neonatal dorsal root ganglia (DRG) using SAGE (serial analysis of gene expression) methodology. Thermo-nociceptors constitute up to 80 % of the neurons in the DRG. In TrkA mutant DRGs, the nociceptor sub-class of sensory neurons is lost due to absence of nerve growth factor survival signaling through its receptor TrkA. Thus, comparison of wild-type and TrkA mutants allows the identification of transcripts preferentially expressed in the nociceptor or mechano-proprioceptor subclasses, respectively. RESULTS: Our comparison revealed 240 genes differentially expressed between the two tissues (P< 0.01). Some of these genes, CGRP, Scn10a are known markers of sensory neuron sub-types. Several potential markers of sub-populations, Dok4, Crip2 and Grik1/GluR5 were further analyzed by quantitative RT-PCR and double labeling with TrkA,-B,-C, c-ret, parvalbumin and isolectin B4, known markers of DRG neuron sub-types. Expression of Grik1/GluR5 was restricted to the isolectin B4+ nociceptive population, while Dok4 and Crip2 had broader expression profiles. Crip2 expression was however excluded from the proprioceptor sub-population. CONCLUSION: We have identified and characterized the detailed expression patterns of three genes in the developing DRG, placing them in the context of the known major neuronal sub-types defined by molecular markers. Further analysis of differentially expressed genes in this tissue promises to extend our knowledge of the molecular diversity of different cell types and forms the basis for understanding their particular functional specificities. [Abstract/Link to Full Text]

Fei Z, Zhang X, Bai HM, Jiang XF, Li X, Zhang W, Hu W
Posttraumatic secondary brain insults exacerbates neuronal injury by altering Metabotropic Glutamate Receptors.
BMC Neurosci. 2007 Nov 17;8(1):96.
ABSTRACT: Background Our previous studies indicated that metabotropic glutamate receptors (mGluRs) are deeply involved in the secondary processes after diffuse brain injury (DBI). In the present study, we used a rodent DBI model to determine whether hypotension exacerbates neuronal injury as a secondary brain insult (SBI) after traumatic brain injury (TBI) by changing the expression of metabotropic glutamate receptors (mGluRs) in the cerebral cortex. Results Three hundred and eleven male Sprague-Dawley rats were randomly assigned into five groups: normal control, sham-operated control, SBI alone, DBI alone, or DBI with SBI. DBI was produced in rats by Marmarou's methods and the SBI model was produced by hypotension. The alteration of neuronal expression of mGluRs after DBI and DBI coupled with SBI was observed by hybridization in situ at different time points in the experiment. We found a higher mortality and neurological severity score (NSS) for rats in the DBI with SBI group compared with those in the DBI alone group. Although there was a significant rise in the expression of group I and group III mGluRs (except mGluR6) and a decrease in the expression of group II mGluRs after DBI (P<0.05), the changes were more severe when DBI was coupled with SBI (P<0.05). The expression of group I mGluRs peaked at 24 hours, while the expression of the group III mGluRs peaked at 6 hours after injuries, which may reflect a self-protection first mechanism of the damaged neurons. Moreover, the overall neuro-harmful effects of mGluRs on neurons were seemly associated with higher mortality and NSS in the DBI with SBI group. Conclusions The results suggest posttraumatic SBI may exacerbate neuronal injury or brain injury by altering expression of mGluRs, and more emphasis should therefore be put on the prevention and treatment of SBI. [Abstract/Link to Full Text]

Qiao X, Lu JY, Hofmann SL
Gene expression profiling in a mouse model of infantile neuronal ceroid lipofuscinosis reveals upregulation of immediate early genes and mediators of the inflammatory response.
BMC Neurosci. 2007 Nov 16;8(1):95.
ABSTRACT: BACKGROUND: The infantile form of neuronal ceroid lipofuscinosis (also known as infantile Batten disease) is caused by hereditary deficiency of a lysosomal enzyme, palmitoyl-protein thioesterase-1 (PPT1), and is characterized by severe cortical degeneration with blindness and cognitive and motor dysfunction. The PPT1-deficient knockout mouse recapitulates the key features of the disorder, including seizures and death by 7-9 months of age. In the current study, we compared gene expression profiles of whole brain from PPT1 knockout and normal mice at 3, 5 and 8 months of age to identify temporal changes in molecular pathways implicated in disease pathogenesis. RESULTS: A total of 267 genes were significantly (approximately 2-fold) up- or downregulated over the course of the disease. Immediate early genes (Arc, Cyr61, c-fos, jun-b, btg2, NR4A1) were among the first genes upregulated during the presymptomatic period whereas immune response genes dominated at later time points. Chemokine ligands and protease inhibitors were among the most transcriptionally responsive genes. Neuronal survival factors (IGF-1 and CNTF) and a negative regulator of neuronal apoptosis (DAP kinase-1) were upregulated late in the course of the disease. Few genes were downregulated; these included the alpha2 subunit of the GABA-A receptor, a component of cortical and hippocampal neurons, and Hes5, a transcription factor important in neuronal differentiation. CONCLUSIONS: A molecular description of gene expression changes occurring in the brain throughout the course of neuronal ceroid lipofuscinosis suggests distinct phases of disease progression, provides clues to potential markers of disease activity, and points to new targets for therapy. [Abstract/Link to Full Text]

Threlkeld SW, Rosen GD, Fitch RH
Age at developmental cortical injury differentially alters corpus callosum volume in the rat.
BMC Neurosci. 2007 Nov 12;8(1):94.
ABSTRACT: BACKGROUND: Freezing lesions to developing rat cortex induced between postnatal day (P) one and three (P1 - 3) lead to malformations similar to human microgyria, and further correspond to reductions in brain weight and cortical volume. In contrast, comparable lesions on P5 do not produce microgyric malformations, nor the changes in brain weight seen with microgyria. However, injury occurring at all three ages does lead to rapid auditory processing deficits as measured in the juvenile period. Interestingly, these deficits persist into adulthood only in the P1 lesion case [1]. Given prior evidence that early focal cortical lesions induce abnormalities in cortical morphology and connectivity [1, 2, 3, 4], we hypothesized that the differential behavioral effects of focal cortical lesions on P1, P3 or P5 may be associated with underlying neuroanatomical changes that are sensitive to timing of injury. Clinical studies indicate that humans with perinatal brain injury often show regional reductions in corpus callosum size and abnormal symmetry, which frequently correspond to learning impairments [5, 6, 7]. Therefore, in the current study the brains of P1, 3 or 5 lesion rats, previously evaluated for brain weight, and cortical volume changes and auditory processing impairments (P21-90), were further analyzed for changes in corpus callosum volume. RESULTS: Results showed a significant main effect of Treatment on corpus callosum volume [F(1,57) = 10.2, P < .01], with lesion subjects showing significantly smaller callosal volumes as compared to shams. An Age at Treatment x Treatment interaction [F(2,57) = 3.2, P < .05], indicated that corpus callosum size decreased as the age of injury decreased from P5 to P1. Simple effects analysis showed significant differences between P1 and P3 [F(1,28) = 8.7, P < .01], and P1 and P5 [F(1,28) = 15.1, P < .001], subjects. Rats with P1 injury resulting in microgyria had the greatest reduction in corpus callosum volume (22% reduction), followed by the P3 group (11% reduction), which showed a significant reduction in corpus callosum volume compared to shams [F(1,31) = 5.9, P < .05]. Finally, the P5 lesion group did not significantly differ from the sham subjects in callosal volume. CONCLUSIONS: Decrements in corpus callosum volume in the P1 and 3 lesion groups are consistent with the reductions in brain weight and cortical volume previously reported for microgyric rats [1, 8]. Current results suggest that disruption to the cortical plate during early postnatal development may lead to more widely dispersed neurovolumetric anomalies and subsequent behavioral impairments [1], compared with injury that occurs later in development. Further, these results suggest that in a human clinical setting decreased corpus callosum volume may represent an additional marker for long-term behavioral outcome. [Abstract/Link to Full Text]

Mitsios N, Saka M, Krupinski J, Pennucci R, Sanfeliu C, Wang Q, Rubio F, Gaffney J, Kumar P, Kumar S, Sullivan M, Slevin M
A microarray study of gene and protein regulation in human and rat brain following middle cerebral artery occlusion.
BMC Neurosci. 2007 Nov 12;8(1):93.
ABSTRACT: BACKGROUND: Altered gene expression is an important feature of ischemic cerebral injury and affects proteins of many functional classes. We have used microarrays to investigate the changes in gene expression at various times-points after middle cerebral artery occlusion in human and rat brain. RESULTS: Our results demonstrated a significant difference in the number of genes affected and the time-course of expression between the two cases. The total number of deregulated genes in the rat was 335 versus 126 in the human, while, of 393 overlapping genes between the two array sets, 184 were changed only in the rat and 36 in the human with a total of 41 genes deregulated in both cases. Interestingly, the mean fold changes were much higher in the human. The expression of novel genes, including p21-activated kinase 1 (PAK1), matrix metalloproteinase 11 (MMP11) and integrase interactor 1, was further analyzed by RT-PCR, Western blotting and immunohistochemistry. Strong neuronal staining was seen for PAK1 and MMP11. CONCLUSION: Our findings confirmed previous studies reporting that gene expression screening can detect known and unknown transcriptional features of stroke and highlight the importance of research using human brain tissue in the search for novel therapeutic agents. [Abstract/Link to Full Text]

Bagley J, Larocca G, Jimenez DA, Urban NN
Adult neurogenesis and specific replacement of interneuron subtypes in the mouse main olfactory bulb.
BMC Neurosci. 2007 Nov 9;8(1):92.
ABSTRACT: BACKGROUND: New neurons are generated in the adult brain from stem cells found in the subventricular zone (SVZ). These cells proliferate in the SVZ, generating neuroblasts which then migrate to the main olfactory bulb (MOB), ending their migration in the glomerular layer (GLL) and the granule cell layer (GCL) of the MOB. Neuronal populations in these layers undergo turnover throughout life, but whether all neuronal subtypes found in these areas are replaced and when neurons begin to express subtypespecific markers is not known. RESULTS: Here we use BrdU injections and immunohistochemistry against interneuron-specific markers (calretinin, calbindin, N-copein, tyrosine hydroxylase and GABA) and show that adult-generated neurons express markers of all major subtypes of neurons in the GLL and GCL. Moreover, the fractions of new neurons that express subtype-specific markers at 40 and 75 days post BrdU injection are very similar to the fractions of all neurons expressing these markers. We also show that many neurons in the glomerular layer do not express NeuN, but are readily and specifically labeled by the fluorescent nissl stain Neurotrace. CONCLUSIONS: The expression of neuronal subtype-specific markers by new neurons in the GLL and GCL changes rapidly during the period from 14-40 days after BrdU injection before reaching adult levels. This period may represent a critical window for cell fate specification similar to that observed for neuronal survival. [Abstract/Link to Full Text]

Pinel P, Thirion B, Meriaux S, Jobert A, Serres J, Le Bihan D, Poline JB, Dehaene S
Fast reproducible identification and large-scale databasing of individual functional cognitive networks.
BMC Neurosci. 2007 Oct 31;8(1):91.
ABSTRACT: BACKGROUND: Although cognitive processes such as reading and calculation are associated with reproducible cerebral networks, inter-individual variability is considerable. Understanding the origins of this variability will require the elaboration of large multimodal databases compiling behavioral, anatomical, genetic and functional neuroimaging data over hundreds of subjects. With this goal in mind, we designed a simple and fast acquisition procedure based on a 5-minute functional magnetic resonance imaging (fMRI) sequence that can be run as easily and as systematically as an anatomical scan, and is therefore used in every subject undergoing fMRI in our laboratory. This protocol captures the cerebral bases of auditory and visual perception, motor actions, reading, language comprehension and mental calculation at an individual level. RESULTS: 81 subjects were successfully scanned. Before describing inter-individual variability, we demonstrated in the present study the reliability of individual functional data obtained with this short protocol. Considering the anatomical variability, we then needed to correctly describe individual functional networks in a voxel-free space. We applied then non-voxel based methods that automatically extract main features of individual patterns of activation: group analyses performed on these individual data not only converge to those reported with a more conventional voxel-based random effect analysis, but also keep information concerning variance in location and degrees of activation across subjects. CONCLUSIONS: This collection of individual fMRI data will help to describe the cerebral inter-subject variability of the correlates of some language, calculation and sensorimotor tasks. In association with demographic, anatomical, behavioral and genetic data, this protocol will serve as the cornerstone to establish a hybrid database of hundreds of subjects suitable to study the range and causes of variation in the cerebral bases of numerous mental processes. [Abstract/Link to Full Text]

Pellissier F, Gerber A, Bauer C, Ballivet M, Ossipow V
The adhesion molecule Necl-3/SynCAM-2 localizes to myelinated axons, binds to oligodendrocytes and promotes cell adhesion.
BMC Neurosci. 2007 Oct 29;8(1):90.
ABSTRACT: BACKGROUND: Cell adhesion molecules are plasma membrane proteins specialized in cell-cell recognition and adhesion. Two related adhesion molecules, Necl-1 and Necl-2/SynCAM, were recently described and shown to fulfill important functions in the central nervous system. The purpose of the work was to investigate the distribution, and the properties of Necl-3/SynCAM-2, a previously uncharacterized member of the Necl family with which it shares a conserved modular organization and extensive sequence homology. RESULTS: We show that Necl-3/SynCAM-2 is a plasma membrane protein that accumulates in several tissues, including those of the central and peripheral nervous system. There, Necl-3/SynCAM-2 is expressed in ependymal cells and in myelinated axons, and sits at the interface between the axon shaft and the myelin sheath. Several independent assays demonstrate that Necl-3/SynCAM-2 functionally and selectively interacts with oligodendrocytes. We finally prove that Necl-3/SynCAM-2 is a bona fide adhesion molecule that engages in homo- and heterophilic interactions with the other Necl family members, leading to cell aggregation. CONCLUSIONS: Collectively, our manuscripts and the works on Necl-1 and SynCAM/Necl-2 reveal a complex set of interactions engaged in by the Necl proteins in the nervous system. Our work also support the notion that the family of Necl proteins fulfils key adhesion and recognition functions in the nervous system, in particular between different cell types. [Abstract/Link to Full Text]

Otten M, Nieuwland MS, Van Berkum JJ
Great expectations: Specific lexical anticipation influences the processing of spoken language.
BMC Neurosci. 2007 Oct 26;8(1):89.
ABSTRACT: BACKGROUND: Recently several studies have shown that people use contextual information to make predictions about the rest of the sentence or story as the text unfolds. Using event related potentials (ERPs) we tested whether these on-line predictions are based on a message-based representation of the discourse or on simple automatic activation by individual words. Subjects heard short stories that were highly constraining for one specific noun, or stories that were not specifically predictive but contained the same prime words as the predictive stories. To test whether listeners make specific predictions critical nouns were preceded by an adjective that was inflected according to, or in contrast with, the gender of the expected noun. RESULTS: When the message of the preceding discourse was predictive, adjectives with an unexpected gender-inflection evoked a negative deflection over right-frontal electrodes between 300 and 600 ms. This effect was not present in the prime control context, indicating that the prediction mismatch does not hinge on word-based priming but is based on the actual message of the discourse. CONCLUSIONS: When listening to a constraining discourse people rapidly make very specific predictions about the remainder of the story, as the story unfolds. These predictions are not simply based on word-based automatic activation, but take into account the actual message of the discourse. [Abstract/Link to Full Text]

Kruger C, Laage R, Pitzer C, Schabitz WR, Schneider A
The hematopoietic factor GM-CSF (Granulocyte-macrophage colony-stimulating factor) promotes neuronal differentiation of adult neural stem cells in vitro.
BMC Neurosci. 2007 Oct 22;8(1):88.
ABSTRACT: BACKGROUND: Granulocyte-macrophage colony stimulating factor (GM-CSF) is a hematopoietic growth factor involved in the generation of granulocytes, macrophages, and dendritic cells from hematopoietic progenitor cells. We have recently demonstrated that GM-CSF has anti-apoptotic functions on neurons, and is neuroprotective in animal stroke models. RESULTS: The GM-CSF receptor alpha is expressed on adult neural stem cells in the rodent brain, and in culture. Addition of GM-CSF to NSCs in vitro increased neuronal differentiation in a dose-dependent manner as determined by quantitative PCR, reporter gene assays, and FACS analysis. CONCLUSIONS: The hematopoietic growth factor GM-CSF stimulates neuronal differentiation of adult NSCs. These data highlight the astonishingly similar functions of major hematopoietic factors in the brain, and raise the clinical attractiveness of GM-CSF as a novel drug for neurological disorders. [Abstract/Link to Full Text]

Franken P, Thomason R, Heller HC, O'Hara BF
A non-circadian role for clock-genes in sleep homeostasis: a strain comparison.
BMC Neurosci. 2007 Oct 18;8(1):87.
ABSTRACT: BACKGROUND: We have previously reported that the expression of circadian clock-genes increases in the cerebral cortex after sleep deprivation (SD) and that the sleep rebound following SD is attenuated in mice deficient for one or more clock-genes. We hypothesized that besides generating circadian rhythms, clock-genes also play a role in the homeostatic regulation of sleep. Here we follow the time course of the forebrain changes in the expression of the clock-genes period (per)-1, per2, and of the clock-controlled gene albumin D-binding protein (dbp) during a 6h SD and subsequent recovery sleep in three inbred strains of mice for which the homeostatic sleep rebound following SD differs. We reasoned that if clock genes are functionally implicated in sleep homeostasis then the SD-induced changes in gene expression should vary according to the genotypic differences in the sleep rebound. RESULTS: In all three strains per expression was increased when animals were kept awake but the rate of increase during the SD as well as the relative increase in per after 6h SD were highest in the strain for which the sleep rebound was smallest; i.e., DBA/2J (D2). Moreover, whereas in the other two strains per1 and per2 reverted to control levels with recovery sleep, per2 expression specifically, remained elevated in D2 mice. dbp expression increased during the light period both during baseline and during SD although levels were reduced during the latter condition compared to baseline. In contrast to per2, dbp expression reverted to control levels with recovery sleep in D2 only, whereas in the two other strains expression remained decreased. CONCLUSIONS: These findings support and extend our previous findings that clock genes in the forebrain are implicated in the homeostatic regulation of sleep and suggest that sustained, high levels of per2 expression may negatively impact recovery sleep. [Abstract/Link to Full Text]

Tsibidis GD, Tavernarakis N
Nemo: a computational tool for analyzing nematode locomotion.
BMC Neurosci. 2007 Oct 17;8(1):86.
ABSTRACT: BACKGROUND: The nematode Caenorhabditis elegans responds to an impressive range of chemical, mechanical and thermal stimuli and is extensively used to investigate the molecular mechanisms that mediate chemosensation, mechanotransduction and thermosensation. The main behavioral output of these responses is manifested as alterations in animal locomotion. Monitoring and examination of such alterations requires tools to capture and quantify features of nematode movement. RESULTS: In this paper, we introduce Nemo (nematode movement), a computationally efficient and robust two-dimensional object tracking algorithm for automated detection and analysis of C. elegans locomotion. This algorithm enables precise measurement and feature extraction of nematode movement components. In addition, we develop a Graphical User Interface designed to facilitate processing and interpretation of movement data. While, in this study, we focus on the simple sinusoidal locomotion of C. elegans, our approach can be readily adapted to handle complicated locomotory behaviour patterns by including additional movement characteristics and parameters subject to quantification. CONCLUSIONS: Our software tool offers the capacity to extract, analyze and measure nematode locomotion features by processing simple video files. By allowing precise and quantitative assessment of behavioral traits, this tool will assist the genetic dissection and elucidation of the molecular mechanisms underlying specific behavioral responses. [Abstract/Link to Full Text]

Lemon CH, Katz DB
The neural processing of taste.
BMC Neurosci. 2007;8 Suppl 3S5.
Although there have been many recent advances in the field of gustatory neurobiology, our knowledge of how the nervous system is organized to process information about taste is still far from complete. Many studies on this topic have focused on understanding how gustatory neural circuits are spatially organized to represent information about taste quality (e.g., "sweet", "salty", "bitter", etc.). Arguments pertaining to this issue have largely centered on whether taste is carried by dedicated neural channels or a pattern of activity across a neural population. But there is now mounting evidence that the timing of neural events may also importantly contribute to the representation of taste. In this review, we attempt to summarize recent findings in the field that pertain to these issues. Both space and time are variables likely related to the mechanism of the gustatory neural code: information about taste appears to reside in spatial and temporal patterns of activation in gustatory neurons. What is more, the organization of the taste network in the brain would suggest that the parameters of space and time extend to the neural processing of gustatory information on a much grander scale. [Abstract/Link to Full Text]

Krimm RF
Factors that regulate embryonic gustatory development.
BMC Neurosci. 2007;8 Suppl 3S4.
Numerous molecular factors orchestrate the development of the peripheral taste system. The unique anatomy/function of the taste system makes this system ideal for understanding the mechanisms by which these factors function; yet the taste system is underutilized for this role. This review focuses on some of the many factors that are known to regulate gustatory development, and discusses a few topics where more work is needed. Some attention is given to factors that regulate epibranchial placode formation, since gustatory neurons are thought to be primarily derived from this region. Epibranchial placodes appear to arise from a pan-placodal region and a number of regulatory factors control the differentiation of individual placodes. Gustatory neuron differentiation is regulated by a series of transcription factors and perhaps bone morphongenic proteins (BMP). As neurons differentiate, they also proliferate such that their numbers exceed those in the adult, and this is followed by developmental death. Some of these cell-cycling events are regulated by neurotrophins. After gustatory neurons become post-mitotic, axon outgrowth occurs. Axons are guided by multiple chemoattractive and chemorepulsive factors, including semaphorins, to the tongue epithelium. Brain derived neurotrophic factor (BDNF), functions as a targeting factor in the final stages of axon guidance and is required for gustatory axons to find and innervate taste epithelium. Numerous factors are involved in the development of gustatory papillae including Sox-2, Sonic hedge hog and Wnt-beta-catenin signaling. It is likely that just as many factors regulate taste bud differentiation; however, these factors have not yet been identified. Studies examining the molecular factors that regulate terminal field formation in the nucleus of the solitary tract are also lacking. However, it is possible that some of the factors that regulate geniculate ganglion development, outgrowth, guidance and targeting of peripheral axons may have the same functions in the gustatory CNS. [Abstract/Link to Full Text]

Boughter JD, Bachmanov AA
Behavioral genetics and taste.
BMC Neurosci. 2007;8 Suppl 3S3.
This review focuses on behavioral genetic studies of sweet, umami, bitter and salt taste responses in mammals. Studies involving mouse inbred strain comparisons and genetic analyses, and their impact on elucidation of taste receptors and transduction mechanisms are discussed. Finally, the effect of genetic variation in taste responsiveness on complex traits such as drug intake is considered. Recent advances in development of genomic resources make behavioral genetics a powerful approach for understanding mechanisms of taste. [Abstract/Link to Full Text]

Kambere MB, Lane RP
Co-regulation of a large and rapidly evolving repertoire of odorant receptor genes.
BMC Neurosci. 2007;8 Suppl 3S2.
The olfactory system meets niche- and species-specific demands by an accelerated evolution of its odorant receptor repertoires. In this review, we describe evolutionary processes that have shaped olfactory and vomeronasal receptor gene families in vertebrate genomes. We emphasize three important periods in the evolution of the olfactory system evident by comparative genomics: the adaptation to land in amphibian ancestors, the decline of olfaction in primates, and the delineation of putative pheromone receptors concurrent with rodent speciation. The rapid evolution of odorant receptor genes, the sheer size of the repertoire, as well as their wide distribution in the genome, presents a developmental challenge: how are these ever-changing odorant receptor repertoires coordinated within the olfactory system? A central organizing principle in olfaction is the specialization of sensory neurons resulting from each sensory neuron expressing only ~one odorant receptor allele. In this review, we also discuss this mutually exclusive expression of odorant receptor genes. We have considered several models to account for co-regulation of odorant receptor repertoires, as well as discussed a new hypothesis that invokes important epigenetic properties of the system. [Abstract/Link to Full Text]

Elsaesser R, Paysan J
The sense of smell, its signalling pathways, and the dichotomy of cilia and microvilli in olfactory sensory cells.
BMC Neurosci. 2007;8 Suppl 3S1.
Smell is often regarded as an ancillary perception in primates, who seem so dominated by their sense of vision. In this paper, we will portray some aspects of the significance of olfaction to human life and speculate on what evolutionary factors contribute to keeping it alive. We then outline the functional architecture of olfactory sensory neurons and their signal transduction pathways, which are the primary detectors that render olfactory perception possible. Throughout the phylogenetic tree, olfactory neurons, at their apical tip, are either decorated with cilia or with microvilli. The significance of this dichotomy is unknown. It is generally assumed that mammalian olfactory neurons are of the ciliary type only. The existence of so-called olfactory microvillar cells in mammals, however, is well documented, but their nature remains unclear and their function orphaned. This paper discusses the possibility, that in the main olfactory epithelium of mammals ciliated and microvillar sensory cells exist concurrently. We review evidence related to this hypothesis and ask, what function olfactory microvillar cells might have and what signalling mechanisms they use. [Abstract/Link to Full Text]

Ferguson C, Hardy SL, Werner DF, Hileman SM, Delorey TM, Homanics GE
New insight into the role of the beta3 subunit of the GABAA-R in development, behavior, body weight regulation, and anesthesia revealed by conditional gene knockout.
BMC Neurosci. 2007;885.
BACKGROUND: The beta3 subunit of the gamma-aminobutyric acid type A receptor (GABAA-R) has been reported to be important for palate formation, anesthetic action, and normal nervous system function. This subunit has also been implicated in the pathogenesis of Angelman syndrome and autism spectrum disorder. To further investigate involvement of this subunit, we previously produced mice with a global knockout of beta3. However, developmental abnormalities, compensation, reduced viability, and numerous behavioral abnormalities limited the usefulness of that murine model. To overcome many of these limitations, a mouse line with a conditionally inactivated beta3 gene was engineered. RESULTS: Gene targeting and embryonic stem cell technologies were used to create mice in which exon 3 of the beta3 subunit was flanked by loxP sites (i.e., floxed). Crossing the floxed beta3 mice to a cre general deleter mouse line reproduced the phenotype of the previously described global knockout. Pan-neuronal knockout of beta3 was achieved by crossing floxed beta3 mice to Synapsin I-cre transgenic mice. Palate development was normal in pan-neuronal beta3 knockouts but ~61% died as neonates. Survivors were overtly normal, fertile, and were less sensitive to etomidate. Forebrain selective knockout of beta3 was achieved using alpha CamKII-cre transgenic mice. Palate development was normal in forebrain selective beta3 knockout mice. These knockouts survived the neonatal period, but ~30% died between 15-25 days of age. Survivors had reduced reproductive fitness, reduced sensitivity to etomidate, were hyperactive, and some became obese. CONCLUSION: Conditional inactivation of the beta3 gene revealed novel insight into the function of this GABAA-R subunit. The floxed beta3 knockout mice described here will be very useful for conditional knockout studies to further investigate the role of the beta3 subunit in development, ethanol and anesthetic action, normal physiology, and pathophysiologic processes. [Abstract/Link to Full Text]

Storozhevykh TP, Senilova YE, Persiyantseva NA, Pinelis VG, Pomytkin IA
Mitochondrial respiratory chain is involved in insulin-stimulated hydrogen peroxide production and plays an integral role in insulin receptor autophosphorylation in neurons.
BMC Neurosci. 2007;884.
BACKGROUND: Accumulated evidence suggests that hydrogen peroxide (H2O2) generated in cells during insulin stimulation plays an integral role in insulin receptor signal transduction. The role of insulin-induced H2O2 in neuronal insulin receptor activation and the origin of insulin-induced H2O2 in neurons remain unclear. The aim of the present study is to test the following hypotheses (1) whether insulin-induced H2O2 is required for insulin receptor autophosphorylation in neurons, and (2) whether mitochondrial respiratory chain is involved in insulin-stimulated H2O2 production, thus playing an integral role in insulin receptor autophosphorylation in neurons. RESULTS: Insulin stimulation elicited rapid insulin receptor autophosphorylation accompanied by an increase in H2O2 release from cultured cerebellar granule neurons (CGN). N-acetylcysteine (NAC), a H2O2 scavenger, inhibited both insulin-stimulated H2O2 release and insulin-stimulated autophosphorylation of insulin receptor. Inhibitors of respiratory chain-mediated H2O2 production, malonate and carbonyl cyanide-4-(trifluoromethoxy)-phenylhydrazone (FCCP), inhibited both insulin-stimulated H2O2 release from neurons and insulin-stimulated autophosphorylation of insulin receptor. Dicholine salt of succinic acid, a respiratory substrate, significantly enhanced the effect of suboptimal insulin concentration on the insulin receptor autophosphorylation in CGN. CONCLUSION: Results of the present study suggest that insulin-induced H2O2 is required for the enhancement of insulin receptor autophosphorylation in neurons. The mitochondrial respiratory chain is involved in insulin-stimulated H2O2 production, thus playing an integral role in the insulin receptor autophosphorylation in neurons. [Abstract/Link to Full Text]

Stins JF, Beek PJ
Effects of affective picture viewing on postural control.
BMC Neurosci. 2007;883.
BACKGROUND: Emotion theory holds that unpleasant events prime withdrawal actions, whereas pleasant events prime approach actions. Recent studies have suggested that passive viewing of emotion eliciting images results in postural adjustments, which become manifest as changes in body center of pressure (COP) trajectories. From those studies it appears that posture is modulated most when viewing pictures with negative valence. The present experiment was conducted to test the hypothesis that pictures with negative valence have a greater impact on postural control than neutral or positive ones. Thirty-four healthy subjects passively viewed a series of emotion eliciting images, while standing either in a bipedal or unipedal stance on a force plate. The images were adopted from the International Affective Picture System (IAPS). We analysed mean and variability of the COP and the length of the associated sway path as a function of emotion. RESULTS: The mean position of the COP was unaffected by emotion, but unipedal stance resulted in overall greater body sway than bipedal stance. We found a modest effect of emotion on COP: viewing pictures of mutilation resulted in a smaller sway path, but only in unipedal stance. We obtained valence and arousal ratings of the images with an independent sample of viewers. These subjects rated the unpleasant images as significantly less pleasant than neutral images, and the pleasant images as significantly more pleasant than neutral images. However, the subjects rated the images as overall less pleasant and less arousing than viewers in a closely comparable American study, pointing to unknown differences in viewer characteristics. CONCLUSION: Overall, viewing emotion eliciting images had little effect on body sway. Our finding of a reduction in sway path length when viewing pictures of mutilation was indicative of a freezing strategy, i.e. fear bradycardia. The results are consistent with current knowledge about the neuroanatomical organization of the emotion system and the neural control of behavior. [Abstract/Link to Full Text]

Zambrano A, Otth C, Mujica L, Concha II, Maccioni RB
Interleukin-3 prevents neuronal death induced by amyloid peptide.
BMC Neurosci. 2007;882.
BACKGROUND: Interleukin-3 (IL-3) is an important glycoprotein involved in regulating biological responses such as cell proliferation, survival and differentiation. Its effects are mediated via interaction with cell surface receptors. Several studies have demonstrated the expression of IL-3 in neurons and astrocytes of the hippocampus and cortices in normal mouse brain, suggesting a physiological role of IL-3 in the central nervous system. Although there is evidence indicating that IL-3 is expressed in some neuronal populations, its physiological role in these cells is poorly known. RESULTS: In this study, we demonstrated the expression of IL-3 receptor in cortical neurons, and analyzed its influence on amyloid beta (Abeta)-treated cells. In these cells, IL-3 can activate at least three classical signalling pathways, Jak/STAT, Ras/MAP kinase and the PI 3-kinase. Viability assays indicated that IL-3 might play a neuroprotective role in cells treated with Abeta fibrils. It is of interest to note that our results suggest that cell survival induced by IL-3 required PI 3-kinase and Jak/STAT pathway activation, but not MAP kinase. In addition, IL-3 induced an increase of the anti-apoptotic protein Bcl-2. CONCLUSION: Altogether these data strongly suggest that IL-3 neuroprotects neuronal cells against neurodegenerative agents like Abeta. [Abstract/Link to Full Text]