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C K Meshul

Publications and source records attributed to C K Meshul.

At least 37 records · Page 2Linked to original sources
PubMed1997

Immunocytochemical analysis of glutamate and GABA in selectively bred mice.

Withdrawal Seizure Prone (WSP) and Withdrawal Seizure Resistant (WSR) mice have been selectively bred for differential ethanol withdrawal handling-induced convulsions (HICs). In addition, it has been observed that WSP mice exhibit drug-naive HICs. This latter finding suggests that WSP and WSR mice differ in their susceptibility to HICs. Alterations in the glutamate and gamma-aminobutyric acid (GABA) systems have been implicated in convulsive activity and have been proposed to underlie the manifestation of ethanol withdrawal symptoms. It is therefore possible that WSP and WSR mice are genetically different with respect to their glutamatergic and/or GABAergic systems. To test this hypothesis, we have analyzed WSP and WSR mice that are both drug- and HIC-naive for differences in the density of nerve terminal glutamate and GABA immunoreactivity within the CA1 subfield of the hippocampus (CA1) and layer II of the somatosensory cortex (SSC). The major finding of this study is that drug- and HIC-naive WSP mice exhibit a significantly greater density of presynaptic glutamate immunoreactivity associated with asymmetric synapses within the CA1, but not the SSC, when compared to WSR mice. The density of GABA immunoreactivity within nerve terminals associated with symmetric synapses does not differ between the selected lines in either brain region. Since prior drug exposure and HICs cannot account for the observed differences in these naive mice, the results strongly suggest that the density of nerve terminal glutamate immunoreactivity within the CA1 is a reflection of inherent genetic differences between WSP and WSR mice. Furthermore, an elevated density of presynaptic glutamate immunoreactivity may be an underlying neurochemical correlate to increased susceptibility to drug-naive and ethanol withdrawal convulsions.

Animals↗
PubMed1997

Methamphetamine alters presynaptic glutamate immunoreactivity in the caudate nucleus and motor cortex.

It has been suggested that methamphetamine (METH)-induced neurotoxicity requires the activation of both dopamine (DA) and glutamate (GLU) systems. To investigate the possibility that METH-induced increases in extracellular GLU, as measured by in vivo microdialysis [Nash and Yamamoto (1992) Brain Res., 581:237-243], arise from neuronal stores, postembedding immunogold electron microscopy was used to measure the density of presynaptic GLU immunoreactivity within the striatum, the shell of the nucleus accumbens, and the motor cortex. Rats were treated with METH (5 mg/kg), or an equivalent volume of saline (SAL), every 2 h for a total of four injections. No ultrastructural evidence of terminal degeneration was observed. Significant decreases in the density of nerve terminal GLU immunolabeling occurred 12 h following METH administration within the primary motor cortex and the ventrolateral caudate/putamen, and a trend towards depletion was seen within the dorsolateral caudate/putamen. Although GLU immunolabeling within the shell of the nucleus accumbens was unaffected, DA content was decreased in all regions examined 1 week following METH treatment. The lack of degeneration, coupled with a partial recovery of DA levels, suggests that moderate doses of METH may inhibit DA biosynthesis without widespread terminal loss. Furthermore, METH administration results in a decrease in presynaptic GLU that correlates both temporally and anatomically with delayed GLU overflow, suggesting that neuronally derived GLU may play a role in METH-induced neurotoxicity. However, there does appear to be a dissociation between DA loss and altered GLU immunocytochemistry within the nucleus accumbens.

Animals↗
PubMed1997

A rat model of chronic pressure-induced optic nerve damage.

To develop unilateral, chronically elevated intraocular pressure in rats, episcleral veins were injected with hypertonic saline and the intraocular pressure was monitored with a Tono-Pen XL tonometer. Histologic analyses of eyes with differing degrees and durations of intraocular pressure elevation were performed to ascertain the effects of these pressures on the optic nerve. Out of 20 consecutive animals, nine had elevations of intraocular pressure following a single injection, while subsequent injections raised intraocular pressure in seven others. One eye became hypotonous. In the remaining animals, subsequent injections sufficient to raise intraocular pressure were deliberately withheld, to determine the possible direct effects of injections on the optic nerve. Mean sustained pressure elevations ranged from 7 to 28 mm Hg and the retinal vasculature remained perfused in all eyes. Optic nerve cross sections from eyes without intraocular pressure elevation appeared identical to those from uninjected eyes, while nerves from eyes with the greatest intraocular pressure rise demonstrated axonal damage that involved 100% of the neural area. Eyes with either less severe pressure elevations or shorter durations showed partial damage, ranging from 0.5% to 10.4% of the neurla area. In 70% of these nerves, damage was concentrated in the superior temporal region. Within the optic nerve head, often associated with astrocytes, axons contained abnormal accumulations of membrane-bound vesicles and mitochondria. The anterior chamber angles showed sclerosis of the trabecular meshwork with anterior synechiae, but Schlemm's canal, collector channels and aqueous veins appeared patent. Unilateral sclerosis of the trabecular meshwork produces sustained elevation of intraocular pressure in rats with optic nerve damage that in many ways resembles that seen in human glaucoma. Understanding the mechanism of nerve damage in this model may provide new insights into the pathogenesis of human glaucoma.

Animals↗
PubMed1996

Characterization and distribution of basic fibroblast growth factor-containing cells in the rat hippocampus.

Basic fibroblast growth factor (bFGF), a member of the heparin-binding growth factor family, is present in relatively high levels in the brain where it may play an important role in the maintenance, repair, and reorganization of the tissue. Although bFGF is associated mainly with astrocytes throughout most of the central nervous system (CNS), a narrow but prominent band of pyramidal neurons, which coincides with the CA2 subregion of Ammon's horn in the hippocampus, stains intensely for bFGF. In order to gain an understanding of which cells express bFGF and whether or not BFGF is a good marker for CA2 neurons, we have used a mouse monoclonal antibody directed against recombinant human bFGF to characterize the distribution and localization of bFGF expression in the hippocampus. We find that about one-quarter of the neurons in CA2 are bFGF positive, and they appear smaller and have more irregular-shaped nuclei than their unstained counterparts. In addition, all glial fibrilary acidic protein (GFAP)-positive astrocytes in the hippocampus stain for bFGF, and the distribution of these astrocytes is heterogeneous in the hippocampus. Finally, in both astrocytes and CA2 pyramidal neurons, bFGF immunoreactivity is localized primarily in the nucleus and to a lesser extent in the cytoplasm and processes of stained cells.

Animals↗
PubMed1996

Activation of corticostriatal pathway leads to similar morphological changes observed following haloperidol treatment.

Treatment with haloperidol, a dopamine receptor D-2 antagonist, for one month resulted in an increase in the mean percentage of asymmetric synapses containing a discontinuous, or perforated, postsynaptic density (PSD) [Meshul et al. (1994) Brain Res., 648:181-195] and a change in the density of striatal glutamate immunoreactivity within those presynaptic terminals [Meshul and Tan (1994) Synapse, 18:205-217]. We speculated that this haloperidol-induced change in glutamate density might be due to an activation of the corticostriatal pathway. To determine if activation of this pathway leads to similar morphological changes previously described following haloperidol treatment, GABA (10(-5) M, 0.5 microliters) was injected into the thalamic motor (VL/VM) nuclei daily for 3 weeks. This treatment resulted in an increase in the mean percentage of striatal asymmetric synapses containing a perforated PSD and an increase in the density of glutamate immunoreactivity within nerve terminals of asymmetric synapses containing a perforated or non-perforated PSD. Subchronic injections of GABA into the thalamic somatosensory nuclei (VPM/VPL) had no effect on the mean percentage of synapses with perforated PSDs but resulted in a small, but significant, increase in density of glutamate immunoreactivity. Using in vivo microdialysis, an acute injection of GABA (10(-5) M, 15 microliters) into VL/VM resulted in a prolonged rise in the extracellular level of striatal glutamate. The increase in asymmetric synapses with perforated PSDs and in glutamate immunoreactivity within nerve terminals of the striatum following either subchronic haloperidol treatment or GABA injections into VL/VM suggest that an increase in glutamate release may be a common factor in these two experiments. It is possible that the extrapyramidal side effects associated with haloperidol treatment may be due, in part, to an increase in release of glutamate within the corticostriatal pathway.

Animals↗
PubMed1996

Correlation of vacuous chewing movements with morphological changes in rats following 1-year treatment with haloperidol.

Long-term treatment with the typical antipsychotic drug, haloperidol, can lead to a sometimes irreversible motor disorder, tardive dyskinesia (TD). It has been hypothesized that increased release of glutamate due to prolonged neuroleptic drug treatment may result in an excitotoxic lesion in specific neuronal populations within the basal ganglia, leading to TD. We reported that treatment with haloperidol for 1 month results in an increase in the mean percentage of striatal asymmetric synapses containing a perforated postsynaptic density (PSD) and that these synapses are glutamatergic. Using quantitative immunocytochemistry, we found that depending on how long the animals had been off haloperidol following subchronic (30 d) treatment, there was either a decrease (1 day off) or increase (3-4 days off) in the density of glutamate immunolabeling within the presynaptic terminals of synapses with perforated PSDs. Using a rat model for TD, animals in the current study were treated for 1 year with haloperidol and spontaneous oral dyskinesias (i.e. vacuous chewing movements, VCMs) were recorded. In these long-term treated animals we wanted to determine if there was a correlation between glutamate function, as measured by changes in synapses with perforated PSDs and the density of nerve terminal glutamate immunoreactivity, and VCM behavior. In drug treated rats which demonstrated either a high or low rate of VCMs, there was a significant increase in the mean percentage of asymmetric synapses in the dorsolateral striatum with perforated PSDs in both haloperidol-treated groups compared to vehicle-treated rats. There was a small but significant increase in the density of glutamate immunolabeling within striatal nerve terminals of the high VCM group compared to the low VCM group. There was, however, no difference in the density of glutamate immunolabeling between the high VCM group compared to the vehicle-treated animals. One reason for this lack of difference was partially due to a significant increase in nerve terminal area within the high VCM group compared to either the low VCM- or vehicle-treated groups. The larger nerve terminal size in the high VCM group may be due to a small but sustained increase in glutamate neurotransmitter release with the ability of the terminal to maintain its supply of glutamate, while the terminals in the low VCM group showed evidence of glutamate depletion. This finding would be consistent with the hypothesis that increased glutamatergic activity may be associated with TD.

Animals↗
PubMed1996

Effects of subchronic clozapine and haloperidol on striatal glutamatergic synapses.

Subchronic treatment with haloperidol increases the number of asymmetric glutamate synapses associated with a perforated postsynaptic density in the striatum. To characterize these synaptic changes further, the effects of subchronic (28 days) administration of an atypical antipsychotic, clozapine (30 mg/kg, s.c.), or a typical antipsychotic, haloperidol (0.5 mg/kg, s.c.), on the binding of [3H] MK-801 to the NMDA receptor-linked ion channel complex and on the in situ hybridization of riboprobes for NMDAR2A and 2B subunits and splice variants of the NMDAR1 subunit were examined in striatal preparations from rats. The density of striatal glutamate immunogold labeling associated with nerve terminals of all asymmetric synapses and the immunoreactivity of those asymmetric synapses associated with a perforated postsynaptic density were also examined by electron microscopy. Subchronic neuroleptic administration had no effect on [3H] MK-801 binding to striatal membrane preparations. Both drugs increased glutamate immunogold labeling in nerve terminals of all asymmetric synapses, but only haloperidol increased the density of glutamate immunoreactivity within nerve terminals of asymmetric synapses containing a perforated postsynaptic density. Whereas subchronic administration of clozapine, but not haloperidol, resulted in a significant increase in the hybridization of a riboprobe that labels all splice variants of the NMDAR1 subunit, both drugs significantly decreased the abundance of NMDAR1 subunit mRNA containing a 63-base insert. Neither drug altered mRNA for the 2A subunit, but clozapine significantly increased hybridization of a probe for the 2B subunit. The data suggest that some neuroleptic effects may be mediated by glutamatergic systems and that typical and atypical antipsychotics can have varying effects on the density of glutamate in presynaptic terminals and on the expression of specific NMDA receptor splice variant mRNAs. Alternatively, NMDAR1 subunit splice variants may differentially respond to interactions with glutamate.

Alternative Splicing↗
PubMed1995

GM1 ganglioside administration partially counteracts the morphological changes associated with haloperidol treatment within the dorsal striatum of the rat.

Haloperidol, a typical antipsychotic drug, causes an increase in the mean percentage of synapses within the situation containing a discontinuous, or perforated, postsynaptic density (PSD) following 1 month of treatment (Meshul et al. 1994). This effect is not observed with the atypical antipsychotic drug, clozapine, following subchronic administration (Meshul et al. 1992a). This morphological change is also associated with an increase in the density of dopamine D2 receptors. The synapses containing the perforated PSD are asymmetrical and the nerve terminals contain the neurotransmitter, glutamate, as demonstrated by immunocytochemistry. We have also shown that subchronic treatment with haloperidol (0.5 mg/kg per day, 30 days) results in a decrease in the density of glutamate immunoreactivity within asymmetric nerve terminals associated with perforated and non-perforated PSDs (Meshul and Tan 1994). This could be due to an increase in glutamate release, perhaps due to activation of corticostriatal synapses. Agnati et el. (1983a) reported that administration of GM1 ganglioside blocks the increase in dopamine D2 receptors following haloperidol treatment. GM1 has also been shown to attenuate the release of glutamate (Nicoletti et al. 1989). In order to determine if similar treatment with ganglioside could block the haloperidol-induced ultrastructural changes notes above, rats were co-administered GM1 (10 mg/kg per day) and haloperidol (0.5 mg/kg per day) for 30 days. We report that GM1 blocked the haloperidol-induced increase in striatal asymmetric synapses containing a perforated PSD, but had no effect on the increase in dopamine D2 receptors or the decrease in nerve terminal glutamate immunoreactivity. GM1, either alone or co-administered with haloperidol, also caused a small, but significant, increase in the density of all asymmetric synapses within the striatum. It is possible that the effect of GM1 in attenuating the haloperidol-induced change in glutamate synapses with perforated PSDs is primarily postsynaptic, since GM1 did not block the change in density of glutamate immunoreactivity within asymmetric nerve terminals.

Animals↗
PubMed1994

Haloperidol-induced morphological changes in striatum are associated with glutamate synapses.

Sub-chronic treatment with the typical neuroleptic, haloperidol (0.5 mg/kg/d, s.c.), but not the atypical neuroleptic, clozapine (35 mg/kg/day, s.c.), causes an increase in synapses containing a perforated postsynaptic density (referred to as 'perforated' synapses) and in dopamine (DA) D2 receptors within the caudate nucleus [46]. To determine if these perforated synapses are glutamatergic, we systemically co-administered MK-801 (0.3 mg/kg/day for 2 weeks), a non-competitive antagonist at the N-methyl-D-aspartate (NMDA) receptor-associated ion channel, and haloperidol. MK-801 blocked the haloperidol-induced increase in striatal perforated synapses, but not the haloperidol-induced increase in DA D2 receptors. Injection of MK-801 into the striatum also attenuated the haloperidol-induced increase in perforated synapses. Post-embedding immuno-gold electron microscopy using antibodies to glutamate indicated that the gold particles were localized within striatal presynaptic nerve terminals that make contact with perforated postsynaptic densities. These findings support the hypothesis that the haloperidol-induced increase in perforated synapses is regulated by the NMDA subtype of excitatory glutamate receptor. The increase in perforated synapses following administration of haloperidol, which is associated with a high incidence of extrapyramidal side effects (EPS), and the lack of a synaptic change following administration of clozapine, known to have a low frequency of EPS, suggests that glutamate synapses play a role in the motoric side effects that are observed with typical neuroleptic drug treatment.

Animals↗
PubMed1994

FNA of extraskeletal myxoid chondrosarcoma: cytomorphologic, EM, and X-ray microanalysis features.

Extraskeletal myxoid chondrosarcoma, an unusual soft tissue lesion which preferentially affects the extremities, is a prime candidate for "pathologist performed" fine-needle aspirates (FNA) because it preferentially affects the extremities [Enzinger and Shiraki, Hum Pathol 1972;3:421-435] and is usually an accessible lesion. Cytomorphologically, the neoplasm consists of clusters of fairly uniform cells, lacking cartilaginous differentiation, with a metachromatic matrix when stained with Diff-Quik (DQ). While subtle, this neoplasm has distinct features and must be distinguished for other neoplasms in the differential diagnosis because patient evaluation, prognosis, and therapy will vary greatly. We present a case characteristic of this tumor in which FNA derived material was subjected to light microscopy, X-ray microanalysis, and immunohistochemical studies; each modality provided data essential to the correct diagnosis.

Aged↗
PubMed1994

Haloperidol-induced morphological alterations are associated with changes in calcium/calmodulin kinase II activity and glutamate immunoreactivity.

Administration of haloperidol for 2 weeks causes an increase within the caudate nucleus of asymmetrical synapses associated with a discontinuous or perforated, postsynaptic density (PSD) [Meshul et al. (1992), Psychopharmacology, 106:45-52; Meshul et al. (1992), Neuropsychopharmacology, 7:285-293]. Coadministration of the N-methyl-D-aspartate noncompetitive antagonist, MK-801, with haloperidol blocked the increase in striatal synapses containing a perforated PSD [Meshul et al. (1994), Brain Res., 648:181-195]. Examination of the caudate using immuno-gold electron microscopy revealed the vast majority (90%) of asymmetrical synapses were labelled with a glutamate antibody [Meshul et al. (1994), Brain Res., 648:181-195]. The purpose of this study was to determine if there were any changes in the density of glutamate immunoreactivity within presynaptic terminals of asymmetric synapses within the striatum following treatment with haloperidol for 1 month that would correlate with the previously observed increase in synapses with perforated PSDs. We also determined the activity of striatal calcium/calmodulin kinase II (CaMK II), an enzyme known to be localized within the synaptic region, after administration of haloperidol. We report here that haloperidol causes an increase in the activity of CaMK II and a decrease in the density of immuno-gold labelling for glutamate within the nerve terminals of asymmetrical synapses containing a perforated or nonperforated PSD. These results are consistent with the hypothesis that the haloperidol-induced increase in activity of CaMK II and the increase in glutamate release, as suggested by the decrease in presynaptic glutamate immunoreactivity, may ultimately lead to an increase in the number of synapses displaying a perforated PSD. These results support the speculation that the haloperidol-induced increase in synapses containing a perforated PSD may be associated with enhanced activity at excitatory synapses.

Animals↗
PubMed1994

Multiple primitive neuroectodermal tumors.

Primitive neuroectodermal tumors are rare, highly aggressive neoplasms that affect both sexes and occur in all age groups. They are a large group of neoplasms with neuroepithelial differentiation, including cutaneous neuroblastomas. Histopathologically they are characterized by a rather uniform population of small, dark cells, with or without Homer Wright rosettes. Immunohistochemically they stain for one or more of the reputed neural markers. Ultrastructurally they show interdigitating processes containing neurosecretory granules, intermediate filaments, and microtubules. We describe a patient with unusual multiple peripheral neuroectodermal tumors localized to the skin, with benign biologic behavior. The patient related the appearance of new lesions for several years without evidence of visceral dissemination or systemic complications. The histopathologic, immunohistochemical, and ultrastructural findings support the diagnosis of a peripheral neuroectodermal tumor.

Diagnosis, Differential↗
PubMed1992

Comparison of chronic intermittent haloperidol and raclopride effects on striatal dopamine release and synaptic ultrastructure in rats.

The effects of chronic intermittent administration (7 months) of two neuroleptics, haloperidol (HAL) and raclopride (RAC), were compared using several different measures. Both drugs were administered weekly by subcutaneous injection at 7.0 mg/kg. Both neuroleptics consistently produced catalepsy throughout the treatment period, although HAL was generally more cataleptogenic than RAC. Assessment of dopamine (DA) release in the caudate putamen (CPu), through the use of in vivo microdialysis, showed that chronic HAL or RAC administration caused a prolonged decrease of DA release in response to a low dose of the DA D2 agonist quinpirole (0.03 mg/kg, sc). Injection of the muscarinic agonist pilocarpine (1.0 mg/kg, IP) did not have any significant within-group effects, although both neuroleptic treatment groups showed decreased DA release when compared to controls. Ultrastructural analysis of the dorsolateral CPu showed that both HAL and RAC treatment resulted in a significant increase in the number of perforated synapses, which contain a discontinuous density along the postsynaptic membrane. These results demonstrate that two different DA D2 receptor antagonists produce a similar effect on DA function and ultrastructural changes within the CPu following chronic, intermittent treatment.

Animals↗
PubMed1992

Effect of haloperidol and clozapine on the density of "perforated" synapses in caudate, nucleus accumbens, and medial prefrontal cortex.

Perforated synapses, which contain a discontinuous density along the postsynaptic membrane, can increase or decrease in numbers following various behavioral and biochemical manipulations. We have previously established that 14-day treatment with haloperidol causes an increase in the number of perforated synapses within the caudate nucleus (dorsolateral region) but not the nucleus accumbens (Meshul and Casey 1989). This effect was reversed if the animals were withdrawn from the drug for an equivalent period of time. We have now further examined the effects of haloperidol administration, which is associated with a high incidence of extrapyramidal side effects (EPS) and tardive dyskinesia (TD), and assessed the effects of clozapine, which appears to have a lower potential for inducing EPS and TD. Administration of haloperidol for 2 weeks significantly increased the percentage of perforated synapses in the caudate, but not in the nucleus accumbens or layer VI of medial prefrontal cortex (MPCx). There was an increase in specific [125I]epidepride binding to D-2 receptors in the caudate nucleus and MPCx following haloperidol. Administration of clozapine for 2 weeks did not affect the percentage of perforated synapses in any of the three dopamine (DA)-rich regions that were examined. There was an increase in specific [3H]SCH 23390 binding to D-1 receptors and in specific [125I]epidepride binding to D-2 receptors only within MPCx following clozapine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Rhabdoid tumor of the skin.

A tumor in the skin of a 42-year-old man was analyzed by light and electron microscopic study and immunohistochemistry. The tumor cells were large and contained eosinophilic, periodic acid-Schiff (PAS)-positive inclusions in the cytoplasm. Immunohistochemically, the neoplasm was positive for intermediate filaments, cytokeratin, vimentin, desmin, and alpha-1-antichimotrypsin, and negative for S-100 and leukocyte common antigen (LCA). Ultrastructurally, the cytoplasm and cellular processes of the cells were inundated with intermediate filaments, some of which were tightly bundled. Junctional complexes and secretory granules were absent. These features suggest a rhabdoid tumor: a malignant tumor of uncertain origin.

Adult↗
PubMed1992

Coadministration of haloperidol and SCH-23390 prevents the increase in "perforated" synapses due to either drug alone.

Perforated synapses, which have a discontinuous density along the postsynaptic membrane, undergo changes in numbers under various experimental conditions. We have previously shown that 14-day administration of haloperidol, a typical neuroleptic which induces extrapyramidal side effects (EPS) and tardive dyskinesia (TD) in patients, causes an increase in the percentage of perforated synapses within the caudate nucleus. This increase was reversed if the animals were taken off the drug for an equal period of time (14 days). There was no effect within the nucleus accumbens. The atypical antipsychotic drug, clozapine, which when administered precipitates a very much lower incidence of EPS and TD, had no effect on the percentage of perforated synapses within either the caudate or nucleus accumbens. Because clozapine binds to both dopamine (DA) D1 and D2 receptors, it was of interest to determine if any changes in perforated synapses occurred following administration of the specific D1 antagonist, SCH-23390. Furthermore, because the action of D2 agonist may be dependent on the activation of the D1 receptor, we asked whether concomitant blockade of the D1 receptor could prevent the increase in perforated synapses due to the action of haloperidol, a drug which upregulates D2 receptors. We found that 14-day treatment with SCH-23390 (1.0 mg/kg per day) or haloperidol (0.5 mg/kg per day) caused an increase in the percentage of perforated synapses within the caudate but not the nucleus accumbens. There was a corresponding increase in DA D1 and D2 receptors in the caudate following administration of SCH-23390 or haloperidol, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Nuclear and cytoplasmic localization of basic fibroblast growth factor in astrocytes and CA2 hippocampal neurons.

Fibroblast growth factors (FGFs) are known to stimulate mitogenesis in a variety of non-neuronal cell types and to support the survival in vitro of many neuronal cell types. The physiological role of FGFs in the CNS is currently not known. The present study determined the distribution in the rat CNS of a prominent member of the FGF family, basic FGF (bFGF). Immunohistochemical analysis showed that bFGF immunoreactivity was found predominantly in astrocytes throughout all regions of the CNS. In contrast, only a few neuronal populations were found to contain bFGF immunoreactivity, most prominent among them, neurons in the CA2 area of the hippocampus. This predominant localization of bFGF to astrocytes was confirmed by two other observations: (1) highly enriched cultures of astrocytes contained bFGF immunoreactivity and bioactivity, whereas highly enriched cultures of cerebral cortical neurons contained no detectable bFGF, and (2) neonatal rat cerebral cortex, which contains only a few differentiated astrocytes, also contained no detectable bFGF immunoreactivity and only low amounts of bFGF bioactivity. Immunocytochemical analysis also suggested that bFGF immunoreactivity was present in the nucleus as well as the cytoplasm of astrocytes and CA2 neurons. This nuclear localization was confirmed by EM analysis of the intracellular distribution of the immunoperoxidase reaction product. In addition, preparations of both nuclear and soluble fractions of brain extracts contained bFGF immunoreactivity and bioactivity. These data suggest that bFGF might be involved in mediating astrocytic influences on the late postnatal maturation and plasticity in the CNS, and that the nuclear localization of bFGF within astrocytes may play an important role in the differentiation of these cells. In addition, bFGF may play a similar role in a few specific neuronal populations, such as CA2 hippocampal neurons.

Animals↗