Pharmacological and second messenger signalling selectivities of cloned P2Y receptors

An autopsy case of a 67-year-old man with typical clinical features of progressive supranuclear palsy (PSP) characterized by impairment of vertical ocular pursuit movement, pseudobulbar palsy, nuchal stiffness, parkinsonism, and dementia is described. In addition to typical pathological changes of PSP, the present case showed fronto-temporal cortical atrophy, accompanied with various Gallyas/tau-positive neuronal and glial structures such as neurofibrillary tangles, pretangle neurons, glial coiled bodies, astrocytic plaques and argyrophilic threads in the cerebral cortex and subcortical nuclei, and many senile plaques throughout the whole cerebral cortex. The present report suggests that PSP and corticobasal degeneration share a common background in neuronal and glial pathologies, that pathological changes of PSP and Alzheimer's disease are mixed in the entorhinal cortex, amygdala. Meynert nucleus, and hypothalamus, and that dementia with frontal lobe-like syndrome in PSP is related to the frontal and temporal cortical pathologies, and is cortical dementia as well as subcortical dementia.     

Low-grade astrocytomas may arise from different astrocyte lineages

The management of low-grade astrocytomas remains a challenge. Although the majority of these tumors have common histological features, they may have very different clinical manifestations and rates of proliferation. Because low-grade astrocytomas are composed of relatively well-differentiated neoplastic cells that closely resemble the astrocytic phenotype, it is possible that some of these lesions express antigens that characterize astrocyte lineages. The authors performed an immunohistochemical analysis of 20 low-grade astrocytomas with A2B5, a monoclonal antibody to a ganglioside found in early postnatal Type 2 (fibrillary) astrocytes, but absent in Type 1 (protoplasmic) astrocytes, and anti-glial fibrillary acidic protein to determine whether the expression of these antigens could be used to determine the histogenesis of these tumors. These findings were compared with the clinical and imaging features of these tumors. The percentages of cells positive for A2B5 and glial fibrillary acidic protein was strongly correlated with the location of the tumor within the cortex or white matter and with the length of preoperative symptoms. Tumors based in the cortex contained significantly fewer A2B5-positive and glial fibrillary acidic protein-positive cells than white matter tumors. In addition, lesions that caused a relatively short period of preoperative symptoms (< 1 year) had significantly more A2B5-positive and glial fibrillary acidic protein-positive cells than lesions responsible for a long preoperative history (mean, 12.9 years). These findings suggest that slow-growing, cortically based low-grade astrocytomas have a phenotype consistent with the Type 1 (protoplasmic) astrocyte lineage, while white matter low-grade astrocytomas express antigens consistent with the Type 2 (fibrillary) astrocyte lineage.     

Astrocytic messenger RNA responses to striatal deafferentation in male rat

This investigation describes the schedule and regional distribution of astrocytic responses in striatum following deafferentation by unilateral frontal cortex ablation. In the ipsilateral deafferented striatum, glial fibrillary acidic protein and clusterin (sulfated glycoprotein-2) messengerRNA showed peak elevations by 10 days postlesioning (Northern blots). Vimentin messengerRNA responded faster, with a transient elevation by three days postlesioning. The messengerRNA for glial fibrillary acidic protein, clusterin and vimentin returned toward control levels by 27 days postlesioning. However, the neuronal marker growth-associated protein messengerRNA, was decreased at all postlesion times. By in situ hybridization, the increased glial fibrillary acidic protein messengerRNA and clusterin messengerRNA signals were localized mainly to the dorsal half of the ipsilateral deafferented striatum and followed the same schedule as found by Northern blots. Glial fibrillary acidic protein messengerRNA was widely diffused in the dorsal striatum and was excluded from fascicles of the internal capsule; a similar distribution was found for glial fibrillary acidic protein-immunopositive astrocytes. While clusterin messengerRNA signal showed a distinct clustering, its immunoreactivity appeared as deposits in the deafferented striatal neuropil; Western blots confirmed the immunocytochemical results. By in situ hybridization, vimentin messengerRNA was mostly localized to the cortical wound cavity dorsal to the deafferented striatum and overlapped the distribution of vimentin-immunopositive cells. These findings suggest a coordination of striatal astrocytic messengerRNA responses with the degeneration of corticostriatal afferents. We also compared these same parameters with those from published reports on the hippocampus after deafferenting lesions. Certain astrocyte molecular responses to deafferentation are detected about five days earlier in the hippocampus than in the striatum. This different schedule in response to decortication may pertain to differences in synaptic remodeling in the hippocampus vs striatum.     

Selective astrocytic transgene expression in vitro and in vivo from the GFAP promoter in a HSV RL1 null mutant vector--potential glioblastoma targeting

Due to the lack of any effective therapy, novel approaches are currently being explored for the treatment of primary brain tumours. It has previously been demonstrated that variants of HSV-1 which are deleted in the RL1 gene and fail to produce the virulence factor ICP34.5 are potential candidates for tumour therapy. The RL1 variant 1716 replicates selectively within tumour cells and has the potential to deliver a therapeutic or tumour killing gene directly to the site of tumour growth. As many intracerebral tumours are glial and predominantly astrocytic in origin, we have evaluated the ability of 1716 to deliver a reporter gene specifically to astrocytes in vivo and in vitro using a 2.2 kb fragment which controls expression of the glial fibrillary acidic protein (GFAP), an astrocyte specific protein. Two 1716 variants, 1774 and 1775, were constructed which contain the GFAP-promoter element linked to the E. coli beta-galactosidase gene, inserted into the HSV-1 UL43 and US5 loci, respectively. In primary cultures, human primary tumour cell lines and established tumour cell lines in vitro, 1774 and 1775 gave high levels of expression of beta-galactosidase specifically in astrocytes. In vivo following intracerebral inoculation, both viruses demonstrated high levels of beta-galactosidase expression predominantly in astrocytes. These results indicate that the GFAP promoter element could be used for efficient and selective transgene delivery to human gliomas.     

Role of glial filaments in cells and tumors of glial origin: a review

In the adult human brain, normal astrocytes constitute nearly 40% of the total central nervous system (CNS) cell population and may assume a star-shaped configuration resembling epithelial cells insofar as the astrocytes remain intimately associated, through their cytoplasmic extensions, with the basement membrane of the capillary endothelial cells and the basal lamina of the glial limitans externa. Although their exact function remains unknown, in the past, astrocytes were thought to subserve an important supportive role for neurons, providing a favorable ionic environment, modulating extracellular levels of neurotransmitters, and serving as spacers that organize neurons. In immunohistochemical preparations, normal, reactive, and neoplastic astrocytes may be positively identified and distinguished from other CNS cell types by the expression of the astrocyte-specific intermediate filament glial fibrillary acidic protein (GFAP). Glial fibrillary acidic protein is a 50-kD intracytoplasmic filamentous protein that constitutes a portion of, and is specific for, the cytoskeleton of the astrocyte. This protein has proved to be the most specific marker for cells of astrocytic origin under normal and pathological conditions. Interestingly, with increasing astrocytic malignancy, there is progressive loss of GFAP production. As the human gene for GFAP has now been cloned and sequenced, this review begins with a summary of the molecular biology of GFAP including the proven utility of the GFAP promoter in targeting genes of interest to the CNS in transgenic animals. Based on the data provided the authors argue cogently for an expanded role of GFAP in complex cellular events such as cytoskeletal reorganization, maintenance of myelination, cell adhesion, and signaling pathways. As such, GFAP may not represent a mere mechanical integrator of cellular space, as has been previously thought. Rather, GFAP may provide docking sites for important kinases that recognize key cellular substrates that enable GFAP to form a dynamic continuum with microfilaments, integrin receptors, and the extracellular matrix.     

Intracerebral injection of interferon-gamma inhibits the astrocyte proliferation following the brain injury in the 6-day-old rat

The present study examines the influence of interferon-gamma (IFN-gamma) on the astrocyte proliferation in the rat brain injured within the early period of postnatal development. Six-day-old male rats received a lesion in the left cerebral hemisphere and a single injection of recombinant rat IFN-gamma into the lesion cavity. One or 2 days after the injury the rats were injected with 3H-thymidine. Brain sections were immunostained for glial fibrillary acidic protein (GFAP), subjected to autoradiography, and examined microscopically to record proliferating GFAP-immunopositive astrocytes labeled with 3H-thymidine. In the IFN-gamma-injected rats, a statistically significant decrease in the intensity of reactive astrocyte proliferation was revealed. On day 1 after injury the intensity of astrocyte proliferation showed dose-dependent changes. Relations between the astrocyte reactivity and multiple factors existing in the injured and IFN-gamma-injected brain are discussed. The results represent the first in vivo evidence of a dose-dependent action of IFN-gamma on the astrocyte proliferation in response to injury.     

The astrocytic response to afferent activity blockade in chick nucleus magnocellularis is independent of synaptic activation, age, and neuronal survival

Astrocytes in nucleus magnocellularis (NM) of the chick respond to afferent activity blockade with increased immunoreactivity for glial fibrillary acidic protein (GFAP). NM neurons respond to the same manipulations with reduced protein synthesis, ribosomal dissociation, and subsequent death of a subset of these neurons. In the present study, we sought to evaluate the relationship between these neuronal and glial responses and to determine if similar activity-dependent mechanisms mediate them. We first examined the anatomical relationship between NM neurons and astrocytic processes by electron microscopy and GFAP immunostaining. Both methods showed that NM neurons deprived of activity for 6 hr were apposed by more glial processes than active NM neurons. However, we found no preferential positioning of GFAP-immunoreactive processes near neurons of the dying or surviving populations, and there were no differences in glial process apposition to dying versus surviving neurons at the EM level. To determine whether the astrocytic response is similar to the neuronal response in age dependence, GFAP immunoreactivity was analyzed in adult chickens following unilateral afferent activity blockade. Unlike the neuronal response to activity blockade, the astrocytic response is equally strong in adult animals. These results imply an independence of the neuronal and astrocytic responses to activity blockade, raising the possibility that these two cell types may be responding to different activity-related signals. This possibility was tested using an in vitro slice preparation. Unilateral stimulation of NM was provided in three ways: orthodromically, antidromically, and orthodromically in a low-calcium medium. The regulation of astrocytic GFAP immunoreactivity by these manipulations of activity was then analyzed. The results of these experiments show that, unlike neuronal protein synthesis, astrocytic GFAP immunoreactivity can be suppressed by either presynaptic or postsynaptic neuronal activity. Therefore, the astrocytes and neurons are regulated by different activity-dependent signals and, by the present measures, their responses to activity blockade appear independent of one another.     

Prenatal and postnatal lead exposure induces 70 kDa heat shock protein in young rat brain prior to changes in astrocyte cytoskeleton

In previous studies we found that chronic postnatal (PN) lead exposure [1 g% (w/v)] induced astroglial hypertrophy in rat hippocampus. Since astrocytic responses change upon the stage during which exposure occurs, astroglial reactions in cerebral cortex and hippocampus of young animals were studied and compared when exposure began during development. Lead-treatment started 90 days prior to mating, and was maintained during gestation and after birth up to PN160. Alterations observed from PN21 to PN140 were assessed by antibodies to the 70kDa heat shock proteins (hsp), glial fibrillary acidic protein (GFAP) and vimentin (VIM) using immunohistochemistry, transmission electron microscopy (TEM), and computer assisted image analysis. The induction of hsp was seen from PN21 to PN45 in non-pyramidal neurons and astrocytes, and at the same time, astroglial swelling was noticed. After PN45 the resolution of this edema coincided with an increase of gliofilaments and GFAP and VIM immunoreaction (PN60-PN90). Recovery of VIM expression persisted after PN120 in the hilus; meanwhile, lipofuscin-like bodies appeared in neurons and astrocytes. Lead exposure during rapid brain growth induced hsp after weaning in neurons and astrocytes prior to astrocyte cytoskeletal changes. Astroglial and neuronal alterations could modify complex neuron-glia interactions, disturbing brain function in consequence.     

Age-induced hypertrophy of astrocytes in rat supraoptic nucleus: a cytological, morphometric, and immunocytochemical study

BACKGROUND: In the adult rat, neuron-astroglia interactions in the supraoptic nucleus (SON) are characterized by the structural and functional plasticity of astrocytes in response to several physiological and experimental conditions. This study has analyzed the plasticity of the supraoptic nucleus astrocytes in response to the age-induced changes in neuronal activity. METHODS: The study was performed in 5-, 12-, 18- and 24-month-old rats. The cytology and organization of astrocytes in the SON were examined using glial fibrillary acidic and vimentin immunocytochemistry and ultrastructural and morphometric analysis. RESULTS: No significant age-related variations in the total number of neurons and astrocytes in the SON were detected, although a few degenerating neurons were found in old rats. An age-dependent increase in GFAP immunoreactivity was observed at the ventral glial lamina, perivascularly and between neuronal perikarya. Vimentin overexpression was also detected in ventral lamina astrocytes with advancing age. At the cell nucleus level, we observed an age-associated increase in nuclear size and in the number of coiled bodies, nuclear bodies, and "cleared" nucleoplasmic areas, as well as changes in the nucleolar organization. At the cytoplasmic level, characteristic ultrastructural features in astrocytes of old rats were the hypertrophy of intermediate filament bundles and the formation of an extensive network of Golgi stacks interlinked by tubulovesicular elements. Glial filaments were often associated with the nuclear envelope and polyribosomes. CONCLUSIONS: The increased GFAP and vimentin immunoreactivity and the morphometric and cytological changes in rat SON astrocytes may reflect a sustained upregulation of cellular activity with age, resulting in hypertrophy of glial perikarya and cell processes. Several factors that are known to influence the expression of the astrocytic phenotype, such as signals produced by degenerating neurons and activated microglia, as well as variations in neuronal activity are considered possible causes of the age-associated changes in SON astrocytes.     

Temporal changes in glial fibrillary acidic protein messenger RNA and [3H]PK11195 binding in relation to imidazoline-I2-receptor and alpha 2-adrenoceptor binding in the hippocampus following transient global forebrain ischaemia in the rat

Immunohistochemical studies have demonstrated that following global forebrain ischaemia the selective neuronal loss that occurs in the CA1 pyramidal cell layer of the hippocampus is accompanied by a reactive astrocytosis, characterized by increases in glial fibrillary acidic protein, and activation of microglia. In this study the spatial changes in glial fibrillary acidic protein messenger RNA levels in the hippocampus have been mapped four, eight, 12, 16 and 20 days following 10 min of global forebrain ischaemia in the rat and related to changes in [3H]PK11195 binding to peripheral benzodiazepine receptors, a putative marker of activated microglia. Recent studies have suggested that the imidazoline-I2-receptor, one of a class of non-adrenergic receptors related to, but structurally and functionally distinct from alpha 2-adrenoceptors, may have a functional role in controlling the expression of glial fibrillary acidic protein. To explore this possibility further we have also mapped changes in imidazoline-I2-receptor and alpha 2-adrenoceptor binding sites. Following transient ischaemia there was a marked, biphasic increase in glial fibrillary acidic protein messenger RNA levels throughout the vulnerable CA1 region of the hippocampus, peaking four days after ischaemia and then increasing gradually during the remainder of the study period. There was also a sustained increase in [3H]PK11195 binding, however, in contrast to the initial increase in glial fibrillary acidic protein messenger RNA levels that peaked four days after ischaemia the density of [3H]PK11195 binding increased rapidly in all strata of the CA1 region over the first eight days and then increased more slowly throughout days 12 to 20. Despite the marked increase in glial fibrillary acidic protein messenger RNA levels there was no concomitant alteration in imidazoline-I2-receptor binding sites detected using the specific radioligand, [3H]2-(2-benzofuranyl)-2-imidazoline, although alpha 2-adrenoceptor binding was decreased at eight days after ischaemia and did not recover. The time-course and biphasic nature of the changes in the astrocytic marker, glial fibrillary acidic protein messenger RNA, in the hippocampus following ischaemia may reflect different functions of glial fibrillary acidic protein-reactive astrocytes in the post-ischaemic period. Differences in temporal expression of glial fibrillary acidic protein messenger RNA and [3H]PK11195 binding support the proposed localization of peripheral benzodiazepine receptors on activated microglia, as distinct from reactive astrocytes. There was no evidence in the present study that imidazoline-I2-receptors are functionally linked to glial fibrillary acidic protein expression as the reactive astrocytosis in the hippocampus following ischaemia was not associated with changes in imidazoline-I2-receptor binding site density.     

Glial organization and chondroitin sulfate proteoglycan expression in the developing thalamus

This study examines the early organization of glial cells, together with the expression of chondroitin sulfate proteoglycans in the developing thalamus of ferrets. Glia were identified with antibodies against vimentin and glial fibrillary acidic protein and the chondroitin sulfate proteoglycans were identified by using an antibody against chondroitin sulfate side chains. Our results reveal three striking features of early thalamic development. First, there is a distinct population of glial fibrillary acidic protein-immunoreactive astrocytes (first seen at E30) that resides in the perireticular thalamic nucleus of the primordial internal capsule. These glial fibrillary acidic protein-immunoreactive astrocytes of the perireticular nucleus are transient and form a conspicuous feature of the early developing forebrain. They are first apparent well before any glial fibrillary acidic protein-immunoreactive astrocytes are seen in other regions of the thalamus (at about P8). Further, unlike in other thalamic regions, these peculiar perireticular astrocytes do not express vimentin before they express glial fibrillary acidic protein. Second, in the reticular thalamic nucleus, the radial glial cells express glial fibrillary acidic protein; they are the only ones to do so in the thalamus during development. The glial fibrillary acidic protein-immunoreactive radial glial cells of the reticular nucleus form a rather distinct band across the developing thalamus at these early stages (E30-P1). Finally, and preceding the expression of glial fibrillary acidic protein, the radial glial cells of the reticular nucleus, unlike those in other thalamic regions, are associated closely with the expression of chondroitin sulfate proteoglycans (E20-E30). Later (after E30), the expression of the chondroitin sulfate proteoglycans in the reticular nucleus declines sharply. The significance of this finding is related to the early organization of the cortico-fugal and cortico-petal pathways.     

The validity of verbal autopsies for assessing the causes of institutional maternal death

We investigated the patterns of degenerative changes of indoleamine-accumulating cells (IACs) induced by 5,7-dihydroxytryptamine (5,7-DHT, 100 microg), and the glial reaction to the neurodegenerative changes of IACs in the cat retina by using light-and electron-microscopy. The neurons accumulating 5,7-DHT in the cat retina were a few ganglion cells and displaced amacrine cells located in the ganglion cell layer (GCL), and some amacrine cells in the inner nuclear layer (INL). The cell density (per unit area, 1 mm2) of the 5,7-DHT accumulating cells in the GCL and INL was 910 and 134 cells, respectively. Most 5,7-DHT accumulating cells showed dark degeneration characterized by widening of the cellular organelles at early stage, and by darkening of the cytoplasm at a late stage. In addition, amacrine cells, showing a typical filamentous degeneration, were observed in a few cases. The degenerated neurons were phagocytosed by microglial cells and astrocytes. The immunoreactivity for glial fibrillary acidic protein (GFAP) in Muller cells was increased at early stage, but thereafter abruptly decreased. In a few cases, severe degenerative changes were observed in Miller cells. These results indicate that 5,7-DHT induces severe dark degeneration of IACs, and most degenerated cells could be eliminated by microglial cells and astrocytes in the cat retina.     

Effects of race, sex, and socioeconomic status upon cardiovascular stress responsivity and recovery in youth

In rat brain, expression of the gap junction protein connexin30 increased during the first 3 weeks after birth and reached its maximum after 4 weeks, as shown by analysis with specific connexin30 antibodies. This contrasts with the prenatal onset of connexin43 expression. On cryosections of rat brain, connexin30 immunoreactivity was found near blood vessels and in ependymal as well as in leptomeningeal cells. Expression in the neuropil was first noticed 3 weeks after birth, showing the same spatial pattern of immunoreactivity as connexin43. This late onset of connexin30 expression in astrocytes was also seen in long-term glial cell cultures, where connexin30 was coexpressed with the astrocytic marker proteins S-100beta and glial fibrillary acid protein. In acute brain slices, connexin30 immunofluorescent signals were detected on processes of functionally identified astrocytes. Thus, our results show that connexin30 is expressed in three different cell types of the rodent brain. The late onset of connexin30 expression in astrocytes suggests that this gap junctional protein fulfills a role in intercellular communication among mature astrocytes.     

Progressive supranuclear palsy

Progressive supranuclear paly (PSP) was firstly reported by Steel in 1964. This condition was separated from Parkinsonism by both clinical symptoms and neuropathological findings. Recently, in an attempt to improve diagnostic accuracy to give appropriate informed concepts and to select correct cases for drug studies or other research purpose, diagnostic criteria for PSP have been developed. PSP begins in the presenile period and duration of illness is 5.9 years (1.2-10.3 years; Maher and Lees, 1986). Cardinal clinical symptoms of PSP are supranuclear gaze palsy, neck dystonia, parkinsonism, pseudobulbar palsy, gait imbalance with frequent falls and subcortical dementia. Supranuclear gaze palsy and bradykinesia are essential for diagnosis. MR-imaging of PSP shows dilatation of the third ventricle. Other laboratory examinations show no specific findings. Neuropathologically, marked dilation of the third ventricle and volume loss of periaqueductal area of the midbrain are noted in macroscopic view. Microscopical examination reveals neuronal loss and gliosis in the tegmentum, the tectum, periaqueductal gray, the dentate-rubro-pallido-luysial area, and the inferior olivary nucleus. Neuropathological hallmarks of PSP are neuronal loss, presence of the globose typed neurofibrillary degeneration, and glial tangles (so called tuft shaped astrocyte and coiled body). Atypical cases of PSP are reported. Such cases are reported as pure akinesia, PSP without ophthalmoplegia, dementia predominant PSP, pathologically diagnosed pallido-nigro-luysial atrophy (PNLA), pathologically diagnosed corticobasal degeneration which showed no laterality, and so on. Reported cases as pure akinesia was diagnosed as PSP or PNLA by neuropathological findings. Improvement of diagnostic accuracy in PSP is expected to ithrapeutic trials, to investigate the etiology, and to separate the other clinical entity from PSP.     

Complement activation accelerates glomerular injury in diabetic rats

A case of hemispheric infarction involving the territory of the right middle cerebral artery and the thalamus showed conspicuous asymmetric degeneration in the substantia nigra, red nuclei, inferior olivary nuclei and dentate nuclei with concomitant changes of progressive supranuclear palsy (PSP). The right substantia nigra and red nucleus showed loss of neurons and proliferation of astrocytes. The right olivary nucleus was hypertrophic, while the neuronal loss and astrocytosis in the dentate nucleus were predominant on the contralateral side. Modified Gallyas-Braak staining revealed the extensive distribution of neurofibrillary tangles (NFTs), threads and intraglial argyrophilic structures in the globus pallidus, subthalamic nuclei, cerebral cortex and dentate nuclei, as well as in the affected brain stem nuclei, with a distinct predominance on the affected side. In this case, the one-sided predominance of the extended degeneration in these brain stem and cerebellar areas is considered, in addition to the PSP changes, to be due to secondary retrograde degeneration via the nigrostriatal and dentato-rubro-thalamic pathways following the hemispheric infarction, and to also be the result of disruption of the dentato-olivary fiber connections. In addition, because of the predominant distribution of NFTs on the more degenerated side, it is surmised that the formation of NFTs may be accelerated by secondary degeneration.     

Glial fibrillary acidic protein-apolipoprotein E (apoE) transgenic mice: astrocyte-specific expression and differing biological effects of astrocyte-secreted apoE3 and apoE4 lipoproteins

The epsilon4 allele of apolipoprotein E (apoE) is associated with increased risk for Alzheimer's disease (AD) and poor outcome after brain injury. In the CNS, apoE is expressed by glia, predominantly astrocytes. To define the potential biological functions of different human apoE isoforms produced within the brain, transgenic mice were generated in which human apoE3 and apoE4 expression is under control of the astrocyte-specific glial fibrillary acidic protein (GFAP) promoter. These animals were then bred back to apoE knock-out mice. Human apoE protein is found within astrocytes and the neuropil throughout development and into the adult period, as assessed by immunocytochemistry and immunoblot analysis in several GFAP-apoE3 and E4 lines. Cultured astrocytes from these mice secrete apoE3 and apoE4 in lipoproteins that are high-density lipoprotein-like in size. When primary hippocampal neurons are grown in the presence of astrocyte monolayers derived from these transgenic mice, there is significantly greater neurite outgrowth from neurons grown in the presence of apoE3-secreting astrocytes compared with apoE4-secreting or apoE knock-out astrocytes. These effects are not dependent on direct astrocyte-neuron contact and appear to require the low-density lipoprotein receptor-related protein. These data suggest that astrocyte-secreted, apoE3-containing lipoproteins have different biological effects than apoE4-containing lipoproteins. In addition to providing information regarding the role of astrocyte-secreted apoE lipoproteins in the normal brain, these animals will also be useful in models of both AD and CNS injury.     

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.