[Sleepiness among adolescents: etiology and multiple consequences]. / La somnolence chez les adolescents: étiologie et conséquences multiples.

Over the past century a dramatic decline in sleep duration among adolescents, such as more than one hour of sleep loss per night, has been reported. A debt in sleep duration could lead to sleep deprivation, a major risk factor associated with daytime sleepiness. Sleepiness refers to the inability to maintain an adequate level of alertness during the day which may result in more or less being able to control falling asleep at inappropriate times. This literature review updates on sleepiness regarding its characteristics, etiology and consequences on adolescents. Studies revealed that from 25 % to 78 % of adolescents had reported sleepiness. Its manifestations may include heavy lids, yawns, difficulties to concentrate and emotional irritability. In addition, while it is recommended that adolescents under 18 years-old should sleep from eight to ten hours a night, only 63 % of them actually do so. The etiology of sleep deprivation and sleepiness in this population can be explained by various biological and societal factors. First, the sleep-wake cycle of adolescents shows a biological shift from the beginning of pubertal maturation, described as a perfect storm. It refers to a social jetlag by going to sleep and waking up later and accumulating a sleep debt during weekdays which they try to reimburse during weekends. This phenomenon can be explained by physiological changes such as a slower accumulation of sleep pressure. In addition to this perfect storm, environmental and societal factors contribute to the social jetlag and reduce sleep duration in adolescents. Screen exposure before bedtime can delay sleep and wake onset, which is a risk factor for sleeping debt. Substance use such as caffeine, cigarettes or electronic vaporizer, ADHD or freely available medication, alcohol, cannabis use or drug consumption could further disrupt sleep-wake cycle by stimulating, depressing or otherwise disrupting the central nervous system. Early, before 8:30 am, class start times have been associated with chronic sleep deprivation, higher level of sleepiness and delayed melatonin peak secretion. Adolescents working or doing extracurricular occupations for more than 20hours a week are more at risk for reduced sleep duration and sleepiness. Parental supervision about sleep during the weekdays were associated with more appropriate bedtime. Adolescents from low socio-demographic characteristics and from minority ethnic groups have reported displaying a shorter sleep duration. Finally, sleep disorders of a physiological origin such as narcolepsy, sleep apnea or restless legs syndrome, may explain the sleep deprivation and sleepiness. Sleep deprivation and sleepiness in adolescents have consequences on their health. Cognitive functioning, such as problem solving, attention or memory, as well as school performance, can be compromised by sleep deprivation and sleepiness. At the psychological level, adolescents reporting sleepiness are more prone to display mental health problems: associations were found between sleepiness and subjective perception of depression, anxiety, somatic complaints as well as with antisocial behaviors. Finally, 68 % of 16 year-old adolescents reported they drove a car, and the reported sleepiness could lead to road accidents due to reduced attentional functioning, reaction time and decision-making abilities. In the United-States, from 7 % to 16.5 % of deadly accidents were related to driving while drowsy. Highlighting etiology and problems associated with sleep deprivation and sleepiness in adolescents could guide researchers and clinicians towards the development of possible interventions. Public health measures and knowledge transfer programs regarding modifiable psychosocial and societal factors associated with sleep-wake bioregulation could increase awareness in parents as well as in political and societal decision makers.

The DSM5/RDoC debate on the future of mental health research: implication for studies on human stress and presentation of the signature bank.

In 2008, the National Institute of Mental Health (NIMH) announced that in the next few decades, it will be essential to study the various biological, psychological and social "signatures" of mental disorders. Along with this new "signature" approach to mental health disorders, modifications of DSM were introduced. One major modification consisted of incorporating a dimensional approach to mental disorders, which involved analyzing, using a transnosological approach, various factors that are commonly observed across different types of mental disorders. Although this new methodology led to interesting discussions of the DSM5 working groups, it has not been incorporated in the last version of the DSM5. Consequently, the NIMH launched the "Research Domain Criteria" (RDoC) framework in order to provide new ways of classifying mental illnesses based on dimensions of observable behavioral and neurobiological measures. The NIMH emphasizes that it is important to consider the benefits of dimensional measures from the perspective of psychopathology and environmental influences, and it is also important to build these dimensions on neurobiological data. The goal of this paper is to present the perspectives of DSM5 and RDoC to the science of mental health disorders and the impact of this debate on the future of human stress research. The second goal is to present the "Signature Bank" developed by the Institut Universitaire en Santé Mentale de Montréal (IUSMM) that has been developed in line with a dimensional and transnosological approach to mental illness.

BLBP-expression in astrocytes during experimental demyelination and in human multiple sclerosis lesions.

Several lines of evidence indicate that remyelination represents one of the most effective mechanisms to achieve axonal protection. For reasons that are not yet understood, this process is often incomplete or fails in multiple sclerosis (MS). Activated astrocytes appear to be able to boost or inhibit endogenous repair processes. A better understanding of remyelination in MS and possible reasons for its failure is needed. Using the well-established toxic demyelination cuprizone model, we created lesions with either robust or impaired endogenous remyelination capacity. Lesions were analyzed for mRNA expression levels by Affymetrix GeneChip® arrays. One finding was the predominance of immune and stress response factors in the group of genes which were classified as remyelination-supporting factors. We further demonstrate that lesions with impaired remyelination capacity show weak expression of the radial-glia cell marker brain lipid binding protein (BLBP, also called B-FABP or FABP7). The expression of BLBP in activated astrocytes correlates with the presence of oligodendrocyte progenitor cells. BLBP-expressing astrocytes are also detected in experimental autoimmune encephalomyelitis during the remission phase. Furthermore, highest numbers of BLBP-expressing astrocytes were evident in lesions of early MS, whereas significantly less are present at the rim of (chronic)-active lesions from patients with long disease duration. Transfection experiments show that BLBP regulates growth factor expression in U87 astrocytoma cells. In conclusion, we provide evidence that expression of BLBP in activated astrocytes negatively correlates with disease duration and in parallel with remyelination failure.

Effects of different dietary ω-6/3 polyunsaturated fatty acids ratios on infarct size and the limbic system after myocardial infarction.

Changes in dietary omega-6/3 polyunsaturated fatty acids (PUFA) ratios affect anti- and proinflammatory equilibrium. As reperfused myocardial infarction (MI) is an inflammatory pathology that alters the cell integrity of the myocardium but also of other tissues, such as the hippocampus and amygdala, attenuation of the inflammation could be helpful in maintaining cell integrity after MI. Therefore, we hypothesized that a decrease in the dietary omega-6/3 PUFA ratio, without altering the diet content in total fat, proteins, or carbohydrates, will result in a reduction of infarct size and a diminution of postreperfusion apoptosis observed in the amygdala and hippocampus. Male Sprague-Dawley rats were fed 1 of 3 diets containing different omega-6/3 PUFA ratios for 2 weeks (5:1; 1:1; 1:5). Then, myocardial ischemia was induced by left anterior descending coronary artery occlusion for 40 min, followed by reperfusion. Cardioprotective mechanisms were studied in the myocardium at 15 min of reperfusion, along with myocardial infarct size after 24 h of reperfusion. Apoptosis was evaluated in the hippocampus and the amygdala. We found that infarct size was significantly reduced by 32% in groups 1:5 and 1:1 vs. group 5:1. Akt activity was higher in groups 1:5 and 1:1 compared with group 5:1. Caspase-3 enzymatic activity doubled in area CA1 and the dentate gyrus (DG) in group 5:1 compared with groups 1:1 and 1:5. In addition, caspase-8 enzymatic activity was increased in the DG at 24 h, and caspase-9 was enhanced in CA1 at 24 h in group 5:1 vs. groups 1:1 and 1:5. These results demonstrate that the increase in the dietary omega-3 PUFA, at the expense of omega-6 PUFA, reduces infarct size and helps to inhibit apoptosis in the limbic system after MI.

Tumor necrosis factor-alpha participates in apoptosis in the limbic system after myocardial infarction.

This study was designed to determine the role of tumor necrosis factor-alpha (TNFalpha) in apoptosis observed in the myocardium and limbic system after myocardial ischemia. PEG sTNFRI, a recombinant, human, soluble p55 Type 1 TNF receptor (3 mg/kg) or vehicle (saline) was administered s.c. to male Sprague-Dawley rats on days 5, 3 and 1 before myocardial ischemia. The animals were then subjected, under anesthesia, to left anterior descending coronary artery occlusion for 40 min, followed by 15-min or 72-h reperfusion. Caspase-3 and -8 activities as well as terminal dUTP nick-end labelling-positive cells were examined in the myocardium (subendocardial and subepicardial regions), lateral (LA) and medial amygdala (MA) and hippocampus (CA1, CA3, dentate gyrus (DG)). After 15 min of reperfusion, the subendocardial and CA1 regions presented an increase in caspase-3 activity, whereas caspase-8 activity appeared to be augmented in the DG. PEG sTNFRI inhibited caspase-8 activation in the DG. After 72 h of reperfusion, plasma TNFalpha levels were reduced in the treated groups. The DG, CA1, CA3 and MA showed an increment of caspase-8 activity, which was reversed by PEG sTNFRI, except in the MA. Furthermore, caspase-3 activity was increased in the CA1, DG, LA and MA. These results indicate that TNFalpha contributes to apoptosis via activation of the extrinsic pathway in the limbic system after myocardial infarction, which is not the case in the myocardium.

The effects of total sleep deprivation on recognition memory processes: a study of event-related potential.

This study examined the memorization of information after a night of normal sleep and total sleep deprivation (TSD) by means of event-related potentials (ERPs). We expected a disfacilitatory effect of TSD on memory processing. Eighteen subjects were tested twice in a counterbalanced fashion. During the study session, subjects were presented with unfamiliar face stimuli and asked to memorize them for a subsequent memory test. At the test session, the subjects were presented with the studied faces intermixed with "new" faces and asked to indicate the previously presented stimuli. The N100 was used as a covariate to control for the differences in level of vigilance between the two sessions. Sleep deprivation decreased subjects' ability to discriminate new from previously studied stimuli and decreased the peak amplitude of the early component (N200) to the decrement of performance. In addition, following TSD the amplitude of the late frontal component (LFC), which is thought to reflect contextual processing, was decreased in covariance with the N100 vigilance component. The amplitude of the late posterior component (LPC/P600) was also reduced but was unrelated to the vigilance component of the ERP. Based on prior studies, this LPC reduction can be interpreted to indicate a decrease in information retrieved after TSD. In summary, a night of TSD decreased the amplitude of the ERPs associated with complex episodic memory task stimuli, affected the frontal cortex during episodic retrieval, and prevented the elaboration process. Furthermore, there was an inability to discriminate what is and what is not in memory, possibly due to less local processing of details.

The ontogeny of alpha-fetoprotein gene expression in the mouse gastrointestinal tract.

The ontogeny of alpha-fetoprotein (AFP) gene expression has been examined in the fetal and adult mouse gastrointestinal tract. AFP mRNA constitutes approximately 0.1% of total mRNA in the fetal gut. The transcripts were localized by in situ hybridization to the epithelial cells lining the villi of the fetal gut. At birth, AFP mRNA declines rapidly to achieve low adult basal levels, which are not affected by different alleles of raf, a gene that determines the adult basal level of AFP mRNA in the liver. The basal level in the adult gut is the consequence of continued AFP transcription in a small number of enteroendocrine cells that are distributed infrequently on the villi. These cells were identified by double antibody staining with antibodies to chromogranin A, an enteroendocrine cell marker and AFP. Previous studies resulted in the generation of a line of transgenic mice containing an internally deleted AFP gene that was greatly overexpressed in the fetal gut. The basis for the inappropriately high level expression of the transgene was shown to be the consequence of very high levels of transcription in the epithelial cells of the villi rather than to expression in inappropriate cell types. The cis-acting DNA sequences required for expression of the AFP gene in the gut were investigated using Caco-2 cells, a human colon adenocarcinoma cell line. These experiments indicated that, with one exception, the regulatory elements required in both the promoter and enhancer regions of the gene coincided with those that are necessary for high level expression in the liver. The one exception was enhancer II, located 5 kbp of DNA upstream of the gene, which exhibited no activity in Caco-2 cells.

Absence of p350 subunit of DNA-activated protein kinase from a radiosensitive human cell line.

The radiosensitive rodent mutant cell line xrs-5 is defective in DNA double-strand break repair and lacks the Ku component of the DNA-activated protein kinase, DNA-PK. Here radiosensitive human cell lines were analyzed for DNA-PK activity and for the presence of related proteins. The radiosensitive human malignant glioma M059J cell line was found to be defective in DNA double-strand break repair, but fails to express the p350 subunit of DNA-PK. These results suggest that DNA-PK kinase activity is involved in DNA double-strand break repair.

Behavioural signs of depression and apoptosis in the limbic system following myocardial infarction: effects of sertraline.

Depression is diagnosed in 15-30% of patients following myocardial infarction (MI) and this may also be observed in the rat. We measured the effects of the antidepressant sertraline on behavioural and biochemical events following MI in a rat model. Following surgery, MI rats and sham controls were treated with sertraline (10 mg/kg, i.p.) or saline. Subgroups of rats were tested for behavioural depression 14 days after surgery. Apoptosis was estimated in other rats by measuring caspase-3 activity and TUNEL positive cells (3 days after surgery) in limbic structures (amygdale, hippocampus, hypothalamus, frontal and prefrontal cortices). Bax/Bcl-2 ratio was measured 14 days after surgery. Behavioural signs of depression (decreased sucrose intake and forced swimming time) were found in saline-treated MI rats but not in sertraline-treated rats. Compared with controls, caspase-3 activity and TUNEL positive cells were significantly increased in most limbic structures of MI rats. High prefrontal Bax/Bcl-2 ratio in MI rats correlated with low forced swimming time. Apoptosis was not found in sertraline-treated MI rats. These results establish the bases of a rat model of depression following MI and show for the first time that a selective serotonin reuptake inhibitor prevents both behavioural and biochemical markers in this model.

Assessment and treatment of pediatric behavioral sleep disorders in Canada.

OBJECTIVES/BACKGROUND: This paper outlines the current state of Canadian training, clinical services, research, and advocacy initiatives related to non-respiratory sleep disorders, with a specific focus on insomnia, the most common sleep problem in children. METHODS: Information for this narrative review was collected from peer-reviewed publications, web-resources, and personal communications and experiences. RESULTS: It is estimated that approximately one-third of Canadian children and youth present with insomnia, and that this is impacting their physical and mental health, as well as learning in school. Training in pediatric sleep is limited and highly inconsistent within and across disciplines. While there are some publicly and privately funded pediatric sleep services available, these are mostly focused on respiratory sleep problems and are not equally accessible across the country. CONCLUSIONS: Pediatric assessment and treatment services for non-respiratory sleep disorders needs to be more integrated into the Canadian health care system.

Apoptosis time course in the limbic system after myocardial infarction in the rat.

Apoptosis is known to occur in the limbic system after myocardial infarction (MI) in the rat. Our study was designed to evaluate the time course dynamics of this phenomenon in limbic areas. Apoptosis, i.e., caspase-3 activity and the number of terminal dUTP nick-end labelling-positive cells, as well as brain-derived neurotrophic factor (BDNF) were quantitated in sham-operated controls and MI rats 1, 2 and 7 days after surgery. Both apoptosis parameters were increased throughout, although in different structures: the CA1 region of the hippocampus and the medial amygdala at day 1, the CA1 region of the hippocampus and the lateral amygdala at day 2, and the frontal cortex at day 7. At day 2, BDNF was decreased in the prefrontal cortex and medial amygdala, whereas it was elevated in the dentate gyrus of the hippocampus; at day 7, BDNF was reduced in the frontal cortex and posterior hypothalamus but was augmented in the medial amygdala. These data indicate that post-MI apoptosis in the limbic system is a dynamic process occurring mainly in the hippocampus and amygdala during the first days after MI. The fact that BDNF was increased as early as 2 days after MI suggests that neurogenesis can occur rapidly in selected limbic regions after MI.

Evolutionary conservation of alternative splicing in chicken.

Alternative splicing represents a source of great diversity for regulating protein expression and function. It has been estimated that one-third to two-thirds of mammalian genes are alternatively spliced. With the sequencing of the chicken genome and analysis of transcripts expressed in chicken tissues, we are now in a position to address evolutionary conservation of alternative splicing events in chicken and mammals. Here, we compare chicken and mammalian transcript sequences of 41 alternatively-spliced genes and 50 frequently accessed genes. Our results support a high frequency of splicing events in chicken, similar to that observed in mammals.

Multiple regulatory elements in the intergenic region between the alpha-fetoprotein and albumin genes.

Three enhancer elements spanning a distance of 7 kilobases have been found at the 5' end of the alpha-fetoprotein (AFP) gene. These elements were identified by transient expression assay after the introduction of a modified mouse AFP gene with variable amounts of 5' flanking sequence into a human hepatoma cell line, Hep G2. These regulatory elements function in a position-independent and orientation-independent manner that is typical of enhancers. All three elements will stimulate transcription from the promoter of the herpes simplex virus thymidine kinase gene. In Hep G2 cells, transcriptional activation from the heterologous promoter was approximately 25- to 50-fold higher than the basal levels obtained in the absence of AFP enhancer elements. In HeLa cells, the increase in thymidine kinase gene transcription varied from 6- to 14-fold, indicating that the enhancer elements exhibit some cell type specificity. Deletion analysis of the region proximal to the AFP transcription initiation site identified an essential region between 85 and 52 bases upstream of the site of initiation of transcription whose removal resulted in almost complete extinction of transcriptional activity. This region, which has been shown to be dispensable for transcription in HeLa cells, defines a second tissue-specific regulatory region in the gene.

Fine-structure mapping of the three mouse alpha-fetoprotein gene enhancers.

Multiple cellular enhancers have been identified previously in the 5'-flanking region of the mouse alpha-fetoprotein gene by transient expression assay. In this report the enhancers have been localized to three regions 200 to 300 base pairs in length at 2.5, 5.0, and 6.5 kilobases of DNA upstream of the transcriptional start site. Nucleotide sequence analysis of the three enhancers revealed areas of homology among them, the most significant of which were two regions of 10 and 18 nucleotides in length. Two of the enhancers were analyzed in detail and shown to be composed of multiple nonidentical domains, none of which was sufficient for full enhancer activity; rather, they acted in an additive fashion in generating the full activity of the enhancer. The tissue-specific activity of the enhancer at -2.5 kilobases was assessed by comparing the activities of subdomains in liver- and non-liver-derived cell lines and was found to be the result of both positive elements within the enhancer and at least one negative element to its 5' end. In contrast, the tissue specificity of the enhancer at -5.0 kilobases was maintained when the minimal essential region was tested alone. The nucleotide sequence similarities, as well as the differences among the enhancers, may explain their differing biological activities both in tissue culture and in vivo.

Involvement of AP-2 in regulation of the R-FABP gene in the developing chick retina.

Little is known regarding the molecular pathways that underlie the retinal maturation process. We are studying the regulation of the retinal fatty-acid-binding protein (R-FABP) gene, highly expressed in retinal precursor cells, to identify DNA regulatory elements and transcriptional factors involved in retinal development. Although the upstream sequence of the R-FABP gene is extremely GC rich, CpG methylation in this region is not implicated in the regulation of this gene because the 5' flanking DNA remains unmethylated with tissue differentiation when there is a dramatic decrease in R-FABP transcript levels. Using a combination of DNase I hypersensitivity experiments, gel shift assays, and DNase I footprinting, we have found three sites of DNA-protein interaction within 205 bp of 5' flanking DNA in the undifferentiated retina and four sites in the differentiated retina. DNA transfection analysis indicates that the first two footprints located within 150 bp of 5' flanking DNA are required for high levels of transcription in primary undifferentiated retinal cultures. The first footprint includes a putative TATA box and Spl binding sites while the second footprint contains a consensus AP-2 DNA binding site. Supershift experiments using antibodies to AP-2 and methylation interference experiments indicate that an AP-2-like transcription factor present in both late-proliferative-stage retina and differentiated retina binds to the upstream region of the R-FABP gene. A combination of data including the expression profile of AP-2 during retinal development and DNA transfection analysis using constructs mutated at critical residues within the AP-2 binding site suggests that AP-2 is a repressor of R-FABP transcription.

Tissue-specific transcription of the mouse alpha-fetoprotein gene promoter is dependent on HNF-1.

Previous work identified four upstream cis-acting elements required for tissue-specific expression of the alpha-fetoprotein (AFP) gene: three distal enhancers and a promoter. To further define the role of the promoter in regulating AFP gene expression, segments of the region were tested for the ability to direct transcription of a reporter gene in transient expression assay. Experiments showed that the region within 250 base pairs of the start of transcription was sufficient to confer liver-specific transcription. DNase I footprinting and band shift assays indicated that the region between -130 and -100 was recognized by two factors, one of which was highly sequence specific and found only in hepatoma cells. Competition assays suggested that the liver-specific binding activity was HNF-1, previously identified by its binding to other liver-specific promoters. Mutation of the HNF-1 recognition site at -120 resulted in a significant reduction in transcription in transfection assays, suggesting a biological role for HNF-1 in the regulation of AFP expression.

Association of human DEAD box protein DDX1 with a cleavage stimulation factor involved in 3'-end processing of pre-MRNA.

DEAD box proteins are putative RNA helicases that function in all aspects of RNA metabolism, including translation, ribosome biogenesis, and pre-mRNA splicing. Because many processes involving RNA metabolism are spatially organized within the cell, we examined the subcellular distribution of a human DEAD box protein, DDX1, to identify possible biological functions. Immunofluorescence labeling of DDX1 demonstrated that in addition to widespread punctate nucleoplasmic labeling, DDX1 is found in discrete nuclear foci approximately 0.5 microm in diameter. Costaining with anti-Sm and anti-promyelocytic leukemia (PML) antibodies indicates that DDX1 foci are frequently located next to Cajal (coiled) bodies and less frequently, to PML bodies. Most importantly, costaining with anti-CstF-64 antibody indicates that DDX1 foci colocalize with cleavage bodies. By microscopic fluorescence resonance energy transfer, we show that labeled DDX1 resides within a Förster distance of 10 nm of labeled CstF-64 protein in both the nucleoplasm and within cleavage bodies. Coimmunoprecipitation analysis indicates that a proportion of CstF-64 protein resides in the same complex as DDX1. These studies are the first to identify a DEAD box protein associating with factors involved in 3'-end cleavage and polyadenylation of pre-mRNAs.

CDK4 amplification is an alternative mechanism to p16 gene homozygous deletion in glioma cell lines.

Recently, it has been shown that a gene encoding the cyclin-dependent kinase 4 inhibitory protein, p16, is frequently targeted for homozygous deletions in several types of tumor cell lines, including those established from malignant gliomas. Here we have examined 32 glioma cell lines for amplification-associated overexpression of the CDK4 gene as an alternative mechanism for abrogating the growth-regulatory effects of p16. Two of the cell lines revealed high-level expression of CDK4 in association with gene amplification, and this alteration was observed among the 10 cases having intact p16 genes. Consequently, 24 of 32 glioma cell lines revealed one of two alternative genetic alterations, each of which indicates that increased cdk4 kinase activity is important to glial tumor development.

The NAD(+) salvage pathway modulates cancer cell viability via p73.

The involvement of the nicotinamide adenine dinucleotide (NAD(+)) salvage pathway in cancer cell survival is poorly understood. Here we show that the NAD(+) salvage pathway modulates cancer cell survival through the rarely mutated tumour suppressor p73. Our data show that pharmacological inhibition or knockdown of nicotinamide phosphoribosyltransferase (NAMPT), a rate-limiting enzyme in the NAD(+) salvage pathway, enhances autophagy and decreases survival of cancer cells in a p53-independent manner. Such NAMPT inhibition stabilizes p73 independently of p53 through increased acetylation and decreased ubiquitination, resulting in enhanced autophagy and cell death. These effects of NAMPT inhibition can be effectively reversed using nicotinamide mononucleotide (NMN), the enzymatic product of NAMPT. Similarly, knockdown of p73 also decreases NAMPT inhibition-induced autophagy and cell death, whereas overexpression of p73 alone enhances these effects. We show that the breast cancer cell lines (MCF-7, MDA-MB-231 and MDA-MB-468) harbour significantly higher levels of NAMPT and lower levels of p73 than does the normal cell line (MCF-10A), and that NAMPT inhibition is cytotoxic exclusively to the cancer cells. Furthermore, data from 176 breast cancer patients demonstrate that higher levels of NAMPT and lower levels of p73 correlate with poorer patient survival, and that high-grade tumours have significantly higher NAMPT/p73 mRNA ratios. Therefore, the inverse relationship between NAMPT and p73 demonstrable in vitro is also reflected from the clinical data. Taken together, our studies reveal a new NAMPT-p73 nexus that likely has important implications for cancer diagnosis, prognosis and treatment.

Correlation of B-FABP and GFAP expression in malignant glioma.

The murine brain fatty acid binding protein (B-FABP) is encoded by a developmentally regulated gene that is expressed in radial glial cells and immature astrocytes. We have cloned the human B-FABP gene and have mapped it to chromosome 6q22-23. We show that B-FABP mRNA is expressed in human malignant glioma tumor biopsies and in a subset of malignant glioma cell lines, as well as in human fetal retina and brain. Malignant glioma tumors are characterized by cytoplasmic bundles of glial fibrillary acidic protein (GFAP), a protein normally expressed in mature astrocytes. Establishment of malignant glioma cell lines often results in loss of GFAP. The subset of malignant glioma cell lines that express GFAP mRNA also express B-FABP mRNA. Co-localization experiments in cell lines indicate that the same cells produce both GFAP and B-FABP. We suggest that some malignant gliomas may be derived from astrocytic precursor cells which can express proteins that are normally produced at different developmental stages in the astrocytic differentiation pathway.