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Biomedical subjects

M Baudry

Publications and source records attributed to M Baudry.

At least 73 records · Page 4Linked to original sources
PubMed1997

Complement and glutamate neurotoxicity. Genotypic influences of C5 in a mouse model of hippocampal neurodegeneration.

Using mice genetically deficient in the complement (C)-system component C5, this study explored a potential novel role of the C-system in Ca(2+)-mediated control of glutamate AMPA receptor functions. We found that Ca2+ preincubation of frozen brain tissue sections enhances AMPA binding capacity more dynamically in C5 deficient (C5-) than congenic C5 sufficient (C5+) mice. The Ca(2+)-mediated response was mostly localized to the CA3 and CA1 subdivisions of the pyramidal layers of the hippocampal formation. In C5- mice, kainic acid (KA) excitotoxicity that models hippocampal neurodegeneration abolished the Ca(2+)-mediated induction of hippocampal AMPA binding. The changes in AMPA binding preceded temporally and overlapped anatomically the appearance of apoptotic features in the same hippocampal neuron layers. C5- mice showed greater hippocampal neurodegeneration then C5+ mice. NMDA binding controlled for specificity of glutamate-mediated changes and found no C5 genotypic influences. The study gives further credence to the role of the C-system in modifying the intensity and outcome during response to conditions leading to hippocampal neurodegeneration.

Animals↗
PubMed1997

Isolation of the gene encoding lamp-1, a lysosomal membrane protein, by differential screening in an animal model of status epilepticus.

The present study employed differential library screening to identify genes associated with kainic acid (KA)-mediated selective neuronal death. One of the isolated clones was lamp-1, which encodes a major lysosomal membrane protein that is also present in the cell membrane. Following systemic KA treatment, lamp-1 was induced in vulnerable hippocampal and other limbic regions. This effect was blocked by cycloheximide (CHX) pre-treatment. Northern blot analysis also demonstrated the presence of lamp-1 transcripts in non-neural tissues. These findings suggest a novel role for lysosomal membrane proteins as markers of selective neuronal vulnerability.

Animals↗
PubMed1997

Molecular cloning of a new unc-33-like cDNA from rat brain and its relation to paraneoplastic neurological syndromes.

Anti-CV2-autoantibodies from patients with paraneoplastic neurological syndromes were used to purify protein(s) related to this disease. A novel cDNA, c-22, was obtained by PCR with primers based on amino-acid sequence of peptides obtained from this protein and rat brain cDNA as template. The deduced amino-acid sequence of c-22 shows homology to the Unc-33 gene from C. elegans in which mutations lead to defects in neuritic outgrowth and axonal guidance and cause uncoordinated movements of the nematode. Several consensus sites for putative protein kinase C phosphorylation were found, suggesting that the c-22 gene product may be a phosphoprotein. Northern hybridizations show that the apparently unique 3.8-kb mRNA of c-22 is present in rat brain tissue and its expression is developmentally regulated: the levels of C-22 mRNA, detectable in brain at embryonic day 17 (E17), increase up to post-natal day 7 (P7) and decline rapidly to an almost undetectable level in adult.

Amino Acid Sequence↗
PubMed1997

Developmental changes in calpain activity, GluR1 receptors and in the effect of kainic acid treatment in rat brain.

The cellular distribution of calpain activation and glutamate receptor 1 (GluR1) subunits of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors and their alterations following kainic acid-induced seizure were evaluated during postnatal development using antibodies specific for spectrin breakdown product and the C-terminus of GluR1 subunits. In the first postnatal week, most brain regions exhibited high levels of calpain activity that progressively decreased during the following weeks. The highest levels of spectrin breakdown product immunoreactivity were observed in the somata and proximal dendrites of hippocampal pyramidal cells, non-pyramidal neurons in stratum oriens, and cortical neurons. In general, during the first two postnatal weeks, kainic acid treatment induced a decrease in spectrin breakdown product immunoreactivity in neuronal cell bodies and an increase in dendritic fields. Obvious elevation in spectrin breakdown product immunoreactivity in selective non-pyramidal cells in stratum oriens started at postnatal day 14, and was further evidenced by postnatal day 21. Likewise, massive calpain activation in subpopulations of neurons in some thalamic nuclei, amygdala, and pyriform cortex was observed after the third postnatal week. GluR1 subunits were highly expressed throughout the forebrain in the first postnatal week, further increased during the second postnatal week, decreased thereafter, and reached adult levels after postnatal day 21. In cortex, intense GluR1 immunostaining was found in the somata and proximal processes of pyramidal and non-pyramidal neurons, with the non-pyramidal neurons in layers IV through VI exhibiting the densest immunolabelling. In the first two postnatal weeks, the somata of hippocampal pyramidal neurons exhibited intense GluR1 immunostaining that became more dendritic in the subsequent developmental period. While hilar cells exhibited a similar developmental pattern as CA regions, the molecular layer of dentate gyrus exhibited weak immunoreactivity from postnatal day 7 to postnatal day 14. The early increase in GluR1 immunoreactivity in hippocampal pyramidal layer following kainic acid treatment occurred throughout the developmental period, while the later decrease in CA regions, amygdala, and pyriform cortex was observed only in postnatal day 21 animals. The combined immunocytochemical studies of spectrin breakdown product localization and GluR1 expression indicate that calpain activation might play an important role in synaptic formation, developmental regulation of synaptic plasticity, and neuronal vulnerability to excitotoxicity during postnatal development. Moreover, calpain-mediated modulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors might underlie these processes.

Animals↗
PubMed1997

Characterization of calpain-mediated proteolysis of GluR1 subunits of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptors in rat brain.

Previous results have indicated that GluR1 subunits of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors are targets of calpain. In the present study, we determined the effects of calpain treatment of synaptic membranes on GluR1 subunits using western blots with antibodies directed against the C-terminal (C-Ab) and the N-terminal (N-Ab) domains of the proteins, and compared them with the effects of calcium treatment of frozen-thawed brain sections. Calpain treatment of synaptic membranes resulted in a large decrease in the GluR1 band (105 kDa) labeled with C-Ab and in the formation of a doublet band labeled with N-Ab due to the appearance of a new species of GluR1 (98 kDa). These effects were blocked almost completely by calpain inhibitors. Calpain-induced changes in GluR1 immunological properties were not associated with modifications of [3H]AMPA or 6-cyano-7-[3H]nitroquinoxaline-2,3-dione ([3H]CNOX) binding. Treatment of frozen-thawed brain sections with concentrations of calcium as low as 0.2 mM resulted in a large decrease in the 105-kDa GluR1 band and in the concurrent appearance of the 98-kDa band. This treatment was associated with increased [3H]-AMPA and [3H]CNOX binding. These results suggest that there exist several types/states of GluR1 subunits exhibiting different sensitivities to calpain. Our data also indicate the existence of additional calcium-dependent processes regulating the characteristics of receptors in intact tissues.

Amino Acid Sequence↗
PubMed1997

NMDA receptor-mediated regulation of AMPA receptor properties in organotypic hippocampal slice cultures.

Activation of the calcium-dependent protease calpain has been proposed to be a necessary step in the formation of long-term potentiation (LTP) in the hippocampus, and stimulation of N-methyl-D-aspartate (NMDA) receptors leads to an increase in intracellular calcium concentration, calpain activation, proteolysis of cytoskeletal elements, and modification of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor properties. In the present study, we evaluated the effects of NMDA treatment of cultured hippocampal slices on the properties of AMPA receptors. Cultured hippocampal slices were treated with NMDA (100 microM) for 15 min and [3H]AMPA binding to membrane fractions was measured. NMDA-treated slices exhibited an increase in both "high-affinity" and "low-affinity" [3H]AMPA binding, with smaller changes in 6-cyano-7-nitro[3H]quinoxaline-2,3-dione binding. The increase in [3H]AMPA binding was significantly reduced by preincubation of cultures with calpain inhibitor I or calpeptin (100 microM). Furthermore, NMDA exposure decreased the number of GluR1 subunits of AMPA receptors detected by an antibody against the C-terminal domain of the subunit in western blots and resulted in the formation of a lower molecular weight species detected by an antibody against the N-terminal domain. Both effects were completely prevented by calpain inhibitors. These results indicate that NMDA receptor activation produces calpain activation and complex modifications of AMPA receptor properties, which could be involved in NMDA receptor-mediated changes in synaptic efficacy.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1996

Effect of phosphatidylserine on the binding properties of glutamate receptors in brain sections from adult and neonatal rats.

The effects of phosphatidylserine (PS) on the binding properties of the AMPA (alpha-amino-3-hydroxy-5-methylisoxazolepropionic acid) and NMDA (N-methyl-D-aspartate) subtypes of glutamate receptors were analyzed by quantitative autoradiography of [3H]AMPA, [3H]6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and [3H]glutamate binding on rat brain tissue sections. Preincubation of brain sections with PS produced an increase in [3H]AMPA binding without modifying the binding properties of [3H]CNQX, an antagonist of AMPA receptors. This effect of PS appeared to be specific for the AMPA subtype of glutamate receptors as the same treatment did not modify [3H]glutamate binding to the NMDA receptors. Furthermore, the PS-induced increase in [3H]AMPA binding was different in various brain structures, being larger in the molecular layer of the cerebellum and almost absent in the striatum. Preincubation with calcium also augmented [3H]AMPA binding, and the lack of additivity of the effects of calcium and PS on [3H]AMPA binding strongly suggests that both treatments share a common mechanism(s) for producing increased agonist binding. Finally, the effect of PS on AMPA receptor properties was markedly reduced in rat brain sections prepared from neonatal rats at a developmental stage that is normally characterized by the absence of LTP expression in certain brain regions. The present data are consistent with the hypothesis that alteration in the lipid composition of synaptic membranes may be an important mechanism for regulating AMPA receptor properties, which could be involved in producing long-lasting changes in synaptic operation.

Animals↗
PubMed1996

Increased expression of cyclin D1 in the adult rat brain following kainic acid treatment.

Recent evidence has implicated aberrant cell cycle regulation as a possible mechanism of apoptosis in non-dividing cells. We previously demonstrated increased expression of the p53 tumor suppressor gene, a prominent cell cycle regulator, in apoptotic neurons. Here we investigated the potential involvement of cyclin D1, a G1 phase cell cycle protein under p53 regulation, in kainic acid-mediated neuronal degeneration. Adult male Sprague-Dawley rats were treated systemically with kainic acid and sacrificed between 1 h and 5 days following seizure onset. Cyclin D1 expression was studied by Western blot analysis and immunohistochemistry using a rabbit polyclonal anti-cyclin D1 antibody. In untreated control rats low levels of cyclin D1 expression were detected in multiple brain regions. Between 8 and 16 h after the onset of kainic acid-induced seizures, increased cyclin D1 immunoreactivity was observed in vulnerable hippocampal pyramidal cells. Five days after seizure onset increased cyclin D1 expression was evident in reactive astrocytes. These results support a role for cyclin D1 in certain neuronal death pathways, and suggest that cyclin D1 has multiple and cell type-specific functions in the central nervous system.

Animals↗
PubMed1996

Polysynaptic potentiation in the lateral septum following stimulation of the fimbria in anesthetized rats.

In anesthetized rats, electrical stimulation of fimbria fibers evoked, in the ipsilateral lateral septum (LS), a field potential consisting of two negative components: an initial negativity (N2-3 complex wave) of high amplitude at 6.7 ms (+/- 0.8 ms; peak latency) and a slow negative wave (N4 wave) of small amplitude at 14.4 ms (+/- 2.4 ms). The N2-3 complex wave represents the monosynaptic activation of LS neurons while the N4 wave corresponds to polysynaptic activation of neurons in the mediolateral part of the LS. In this study, we investigated the effects of high-frequency stimulation of fimbria fibers on LS field potentials and compared them with those observed in the CA3 area. Tetanic stimulation of the fimbria did not change the characteristics of the N2-3 wave but induced a long-lasting increase in amplitude and slope of the N4 wave. A positive correlation was found between the magnitude of CA3 LTP and lateral septal polysynaptic potentiation of the N4 component. These results indicate that patterns of stimulation delivered to the same input fibers (fimbria fibers) produce similar changes in a polysynaptic input to the LS and in a monosynaptic input to the CA3 and emphasize the complexity of signal processing in serial networks.

Anesthesia↗
PubMed1996

Two synaptotagmin genes, Syt1 and Syt4, are differentially regulated in adult brain and during postnatal development following kainic acid-induced seizures.

The synaptotagmins together with other vesicle proteins are thought to be essential for the docking and/or fusion of synaptic vesicles with the plasma membrane that occurs following depolarization and calcium influx in presynatic terminals. Syt4, the fourth identified member of the synaptotagmin family, is inducible in PC12 cells by depolarization and secretagogues, and in limbic regions of the adult rat brain by kainic acid-induced seizures. In the present study, we examined the time course of the seizure-induced changes in the expression of Syt4 and Syt1, both in adult animals and during the postnatal period. Syt4 was transiently induced in several structures of the adult rat brain following seizure activity with peak inductions between 4 and 8 h and overal return to control values by 30 h. No induction was observed following seizure activity in 7-day-old animals. The brain regions most sensitive to increased induction were, in decreasing order of sensitivity, hippocampal pyramidal cells dentate granule cells and piriform cortex pyramidal cells. The brain areas showing the greatest Syt4 stimulation in adults were also the areas in which Syt4 was induced by seizures earlier in development. In contrast, Syt1 mRNA was depressed in adult brains following seizure activity, particularly in the dentate granule cells. Our results suggest that the differential regulation of different synaptotagmin genes following excessive neuronal activity might participate in rapid adaptation of subsequent transmitter release.

Animals↗
PubMed1996

Involvement of the 12-lipoxygenase pathway of arachidonic acid metabolism in homosynaptic long-term depression of the rat hippocampus.

Low-frequency stimulation is associated with long-term depression (LTD) of synaptic efficacy in various brain structures. Like long-term potentiation (LTP), homosynaptic LTD in area CA1 of the hippocampus appears to require NMDA receptor activation, changes in postsynaptic calcium concentration and phospholipase A2 (PLA2) activation. Arachidonic acid (AA) is released after the activation of calcium-dependent phospholipases and free AA is rapidly metabolized to a family of bioactive products (the eicosanoids) which are thought to be both intracellular and extracellular messengers. In the present study, we investigated the involvement of the cyclooxygenase and lipoxygenase pathways of AA metabolism in the formation of homosynaptic LTD in the rat hippocampus. Stimulation at 1 Hz for 15 min was used to produce homosynaptic depression in area CA1 of hippocampal slices. LTD induction was partially blocked by bromophenacyl bromide (50-100 microM), a selective PLA2 inhibitor, and by the a nonselective lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA; 100 microM). In contrast, the specific cyclooxygenase blocker indomethacin (100 microM) did not significantly reduce hippocampal LTD. Since NDGA interferes with LTD formation, we examined whether specific inhibitors of 5- and 12-lipoxygenases were capable of blocking LTD expression. The 12-lipoxygenase inhibitor baicalein at a concentration of 50 microM reduced LTP formation when given in the bath, an effect that was less pronounced with the 5-lipoxygenase inhibitor AA-861. These data suggest that the activation of endogenous PLA2 and the formation of 12-lipoxygenase metabolites of AA may be important factors controlling the expression of hippocampal LTD.

Acetophenones↗
PubMed1996

Regional distribution and time-course of calpain activation following kainate-induced seizure activity in adult rat brain.

Systemic injection of kainic acid (KA) in adult rat elicits a pattern of neuronal pathology which exhibits several features of human temporal lobe epilepsy. KA-induced seizure activity is accompanied by the activation of the calcium-dependent protease calpain in limbic structures. In the present study, we evaluated the spatio-temporal activation of calpain after the onset of seizure activity by immunohistochemistry using an antibody for the spectrin breakdown product (sbdp) generated by calpain-mediated spectrin proteolysis. In addition, we compared the changes in sbdp immunoreactivity with those in immunoreactivity to subunits of the Glu/AMPA receptors (GluR1 and GluR2/3). One hour after seizure onset, sbdp accumulation was observed in selected interneurons in stratum oriens and in the hilus of the dentate gyrus. By 4 h, sbdp immunoreactivity was prominent in dendritic fields of the hippocampus as well as in neurons in thalamus and piriform cortex. By 8 h, sbdp immunoreactivity had disappeared from interneurons but was localized in pyramidal cell bodies in hippocampus. Intense labeling of cell bodies and dendritic fields persisted until 5 days following KA treatment. Changes in GluR subunit immunoreactivity were mirror images of those seen for sbdp. In general, increased sbdp immunoreactivity in dendritic fields was associated with decreased GluR1 immunoreactivity. However, increased sbdp immunoreactivity in neuronal perikarya was also associated with increased GluR immunoreactivity. These results indicate that calpain activation following seizure onset exhibits a specific spatio-temporal pattern, with activation in restricted interneurons preceding widespread activation in pyramidal neurons. Calpain activation also precedes neuronal pathology and could thus represent an initial trigger for neuronal pathology. Finally, the results suggest that calpain activation produces rapid alterations in GluR subunit properties which could be involved in the hyperexcitability observed following seizure activity.

Animals↗
PubMed1996

Developmental changes in depolarization-mediated AMPA receptor modifications and potassium-induced long-term potentiation.

In the present study, we examined the KCl-induced increase in [3H] amino-3-hydroxy-5-methylisoxazole-4-propionate ([3H]AMPA) binding in telencephalic synaptoneurosomes and potentiation of synaptic transmission (KLTP) in hippocampal slices during development in rats. As previously reported, KCI-induced depolarization of telencephalic synaptoneurosomes resulted in a 40 +/- 5% increase in [3H]AMPA binding to membrane fractions in adult rats (3 months old). KCI-induced increase in [3H]AMPA binding was reduced to 24 +/- 5% and 15 +/- 5% at postnatal days (PND) 25-30 and PND 15-20 respectively, and was only 6 +/- 5% at PND 5-10. KLTP in area CA1 of hippocampus was most pronounced in adult slices (40 +/- 5%), and was reduced to 30 +/- 5% in slices prepared from PND 25-30 animals; KCI-induced LTP was absent in CA1 hippocampal slices prepared from PND 5-10 animals (3 +/- 5%). The decrease in KCI-induced changes in AMPA receptor binding in young animals was also associated with an altered capacity of the bee venom peptide, mellitin (a phospholipase A2 (PLA2) activator), to increase [3H]AMPA binding in synaptoneurosomes. The smaller effect of mellitin on [3H]AMPA binding in young animals was not due to a decreased ability of this peptide to release [3H]arachidonate from synaptoneuro-somes. The parallel modifications in the extent of depolarization-induced change in AMPA receptor binding and excitatory synaptic transmission during development further support the hypothesis that alterations in AMPA receptor properties may play a critical role in synaptic plasticity.

Age Factors↗
PubMed1996

beta-Amyloid toxicity in organotypic hippocampal cultures: protection by EUK-8, a synthetic catalytic free radical scavenger.

Oxygen free radicals have been proposed to mediate amyloid peptide (beta-AP)-induced neurotoxicity. To test this hypothesis, we evaluated the effects of EUK-8, a synthetic catalytic superoxide and hydrogen peroxide scavenger, on neuronal injury produced by beta-AP in organotypic hippocampal slice cultures. Cultures of equivalent postnatal day 35 (defined as mature) and 14 (defined as immature) were exposed to various concentrations of beta-AP (1-42 or 1-40) in the absence or presence of 25 microM EUK-8 for up to 72 hours. Neuronal injury was assessed by lactate dehydrogenase release and semiquantitative analysis of propidium iodide uptake at various times after the initiation of beta-AP exposure. Free radical production was inferred from the relative increase in dichlorofluorescein fluorescence, and the degree of lipid peroxidation was determined by assaying thiobarbituric acid-reactive substances. Treatment of mature cultures with beta-AP (50-250 microg/ml) in serum-free conditions resulted in a reproducible pattern of damage, causing a time-dependent increase in neuronal injury accompanied with formation of reactive oxygen species. However, immature cultures were entirely resistant to beta-AP-induced neurotoxicity and also demonstrated no dichlorofluorescein fluorescence or increased lipid peroxidation after beta-AP treatment. Moreover, mature slices exposed to beta-AP in the presence of 25 microM EUK-8 were significantly protected from beta-AP-induced neurotoxicity. EUK-8 also completely blocked beta-AP-induced free radical accumulation and lipid peroxidation. These results not only support a role for oxygen free radicals in beta-AP toxicity but also highlight the therapeutic potential of synthetic radical scavengers in Alzheimer disease.

Amyloid beta-Protein Precursor↗
PubMed1996

Hereditary deficiencies in complement C5 are associated with intensified neurodegenerative responses that implicate new roles for the C-system in neuronal and astrocytic functions.

Possible roles of the complement (C) system in the normal and injured brain were explored with inbred mice that carried a frameshift mutation in the C5 gene. A congenic pair was used: the C5-sufficient (C5+) B10.D2/nSnJ strain with the functional allele (Hc1) from the C57BL/10J donor strain was compared with the C5-deficient (C5-) B10.D2/oSnJ with the Hc0 allele from the C5-deficient DBA/2J donor strain. In response to the excitotoxin kainic acid (KA), C5- mice had more hippocampal pyramidal neuron death and greater induction of astrocyte mRNAs (GFAP, apoE, apoJ). In primary astrocyte cultures from unlesioned mice, an inflammatory stimulus (LPS) caused greater production of IL-6 and TNF production in C5- mice. These enhanced responses to KA and LPS suggest that hereditary C5 deficits modify responses to neurodegenerative stimuli of neurons and astrocytes. Moreover, unlesioned C5- mice had smaller input-output slopes for the NMDA component of the EPSP amplitude, but enhanced the Ca(+2)-dependent AMPA binding. Thus, C5 deficits also modify basal properties of glutamatergic neurotransmission that pertain to synaptic plasticity. These findings are also discussed in relation to roles of the C-system in Alzheimer disease (AD). C5 deficiencies may also be considered in the choice of strains as transgene hosts and for genetic analysis of normal and pathological brain functions. In recent transgenic studies for AD, C5- hosts showed greater neurodegeneration, consistent with the present data. These pleiotropic associations of C5 deficiency indicate roles for the C-system in neurodegeneration, but also in normal neural functions.

Animals↗
PubMed1996

The C-terminal domain of glutamate receptor subunit 1 is a target for calpain-mediated proteolysis.

The AMPA receptors are glutamate-gated ion channels mediating synaptic transmission at the majority of excitatory synapses in the mammalian CNS. They are composed of four subunits (GluR1-4) which exist in two alternatively spliced variants (flip and flop) and are generally considered to form pentameric receptors. The transmembrane structure of the receptors remains a matter of controversy as some data suggest a transmembrane topology consisting of five, four, or three membrane spanning regions. Some receptor properties have been shown to be regulated by phosphorylation processes as well as by the phospholipid environment. More recently, we have shown that calcium treatment of thin (10 microns) frozen-thawed brain sections resulted in profound modifications of the immunochemical properties of the AMPA receptors. More specifically, immunolabelling of the AMPA receptors with antibodies directed against the C-terminal domain of GluR1 and GluR2/3 was markedly decreased in dendritic fields following such treatment at 35 degrees C. This effect was temperature-dependent and completely blocked by inhibitors of the calcium-dependent proteases calpains, and we suggested that calpains are involved in the regulation of AMPA receptor properties. The results of the present study demonstrate that calpain activation produces a partial proteolysis in the C-terminal domain of the receptors and generates a new receptor species with an apparent molecular weight of 103,000 mol. wt. Sequence analysis of the GluR1 C-terminal domain suggests a couple of cleavage sites for calpains. These results are of particular interest considering the body of evidence implicating calpains and changes in excitatory amino acid receptors in mechanisms of synaptic plasticity as well as in neurodegenerative processes.

Blotting, Western↗
PubMed1996

Induction of glucose-regulated protein (glucose-regulated protein 78/BiP and glucose-regulated protein 94) and heat shock protein 70 transcripts in the immature rat brain following status epilepticus.

Prior to 21 days of age, the immature rat brain is relatively resistant to excitotoxicity caused by the glutamate analogue, kainate. As stress-inducible proteins (GRP78, GRP94 and HSP70) have been proposed to possess molecular chaperone activity and protect cells from the deleterious effects of damaged proteins, we examined the pattern of expression of their respective messenger RNAs following systemic kainate at different postnatal ages. In untreated rats between seven and 21 days old, there was a higher basal level of grp78 and grp94 expression compared to hsp70. Unlike hsp70, which was inducible only in 21-day-old rats, kainate-mediated grp94 induction occurred in several regions of the brain as early as postnatal day 7. Grp78 messenger RNA expression was also increased by kainate treatment in 14-day-old rats, and the induction was most pronounced in the kainate-resistant dentate gyrus. With increasing age, longer lasting expression of both grp78 and grp94 messenger RNAs was observed in kainate-vulnerable regions, similar to observations in the adult rat brain. These results demonstrate non-overlapping expression patterns of glucose-regulated proteins and HSP70 in the immature central nervous system, suggesting that they serve different functions. While hsp70 induction could be a marker for potential cell injury and death, increased expression of grp78 and grp94 could play a neuroprotective role in the developing rat brain.

Animals↗