Heat Shock Protein HSP70 Increases the Resistance of Cortical Cells to Glutamate Excitotoxicity

I. P. Pavlov Institute of Physiology, Russian Academy of Sciences
Bulletin of Experimental Biology and Medicine (Impact Factor: 0.36). 08/2005; 140(1):1-5. DOI: 10.1007/s10517-005-0396-x
Source: PubMed


Preincubation of cultured slices of the olfactory cortex of rat brain with heat shock protein in a concentration of 1 microg/ml protected the pre- and postsynaptic mechanisms of glutamatergic synaptic transmission from glutamate excitotoxicity (50 mM) inducing blockade of excitatory postsynaptic function and reducing presynaptic processes. It was hypothesized that heat shock protein protects AMPA and NMDA receptor-mediated processes.

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    • "The chaperone Hsp70, which is also induced by ischemia [106], has a role in the protection of NMDA receptors and as such contributes to their normal function in toxic conditions. It also protects the presynaptic terminal by maintaining ion channel proteins in the presence of toxic levels of glutamate [107]. The endoplasmic reticulum associated GRP78, in turn, is responsible for maintaining the levels of intracellular calcium despite the insult, as hippocampal neurons treated with siRNA designed to inactivate GRP78 displayed higher levels of intracellular calcium upon glutamate treatment than control neurons, which is consistent with a role of calcium from the endoplasmic reticulum in excitotoxicity [108]. "
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    ABSTRACT: ABSTRACT: Stroke, a major cause of disability and mortality in the elderly, occurs when a cerebral blood vessel is occluded or ruptured, resulting in ischemic damage and death of brain cells. The injury mechanism involves metabolic and oxidative stress, excitotoxicity, apoptosis and inflammatory processes, including activation of glial cells and infiltration of leukocytes. In animal models, dietary energy restriction, by daily calorie reduction (CR) or intermittent fasting (IF), extends lifespan and decreases the development of age-related diseases. Dietary energy restriction may also benefit neurons, as suggested by experimental evidence showing that CR and IF protect neurons against degeneration in animal models. Recent findings by our group and others suggest the possibility that dietary energy restriction may protect against stroke induced brain injury, in part by inducing the expression of neurotrophic factors, such as brain-derived neurotrophic factor (BDNF) and basic fibroblast growth factor (bFGF); protein chaperones, including heat shock protein 70 (Hsp70) and glucose regulated protein 78 (GRP78); antioxidant enzymes, such as superoxide dismutases (SOD) and heme oxygenase-1 (HO-1), silent information regulator T1 (SIRT1), uncoupling proteins and anti-inflammatory cytokines. This article discusses the protective mechanisms activated by dietary energy restriction in ischemic stroke.
    Experimental and Translational Stroke Medicine 09/2011; 3(1):8. DOI:10.1186/2040-7378-3-8
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    • "Exo-Hsp70/Hsc70 in chemically-induced seizures | 1039 cesses from glutamate excitotoxicity (Mokrushin et al. 2005). We suggested that the anticonvulsant effects exerted by Hsp70/Hsc70 are related to its ability to migrate into NMDA receptor-rich areas of the brain. "
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    ABSTRACT: J. Neurochem. (2010) 115, 1035–1044. Heat shock protein 70 kDa (Hsp70) possesses a remarkable neuroprotective activity and the results of recent studies demonstrated its efficacy in the attenuation of epileptic seizures. The aim of this study was to explore the effects of a pure Hsp70/Hsc70 preparation delivered to the brain regions involved in generalized seizures induced in rats by intracerebroventricular microinjections of NMDA or systemic injections of pentylenetetrazole. Purified Hsp70/Hsc70 was administered (intracerebroventricular) 2 h before the induction of seizures. Compared to the vehicle-treated control animals, Hsp70/Hsc70-pretreated rats demonstrated reduced severity of NMDA- and pentylenetetrazole-induced seizures. To identify the brain structures potentially implicated in the Hsp70/Hsc70-mediated anticonvulsant effect, we analysed the localization of a fluorescently-labelled chaperone in the brain. Labelled Hsp70/Hsc70 was found in neurons and terminals of the limbic seizure complex of the brain and was co-localized in these regions with NMDA receptors, synaptophysin and the GABA-synthesizing enzyme, L-glutamic acid decarboxylase 67. An immunoprecipitation assay confirmed interactions between Hsp70 and both synaptophysin and L-glutamic acid decarboxylase 67 in brain tissue. We suggest that the anticonvulsant effect of exogenous Hsp70/Hsc70 is not only based on its protective capacity but is also related to its ability to modulate GABA neurotransmission, which in turn contributes to the maintenance of the excitatory-inhibitory balance of the CNS.
    Journal of Neurochemistry 11/2010; 115(4):1035-44. DOI:10.1111/j.1471-4159.2010.06989.x · 4.28 Impact Factor
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    • "Several studies have shown that Hsp70 expression is a good marker of changes in metabolic activity in hippocampus neurons because they are increased by psychophysiological stress and training [1] [27]. It has been reported that pre-incubation with Hsp70 protects slices of olfactory cortex from glutamate excitotoxicity [21]. Moreover, it was suggested that Hsp70 would be a mediator of volume signal transmission in the olfactory cerebral cortex of rats and would be involved in the development and retention of long-term potentiation [22]. "
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    ABSTRACT: Heat-shock proteins (Hsp) are synthesized in the central nervous system in response to traumas but also after physical exercise and psychophysiological stress. Therefore, an increase in Hsp expression is a good marker of changes in metabolic activity. In the crab Chasmagnathus, a powerful memory paradigm has been established. Memory modulation is possible by water shortage. The brain areas activated by either training protocols and/or water-deprivation are still unknown. Hsp expression might be a marker to sensing the increase in metabolic activity in crab Chasmagnathus brain neuropils engaged in the physiological responses triggered by water deprivation and cognitive processing. Here, we observed an increase in brain Hsp of 70kDa (Hsp70) expression after a heat-shock treatment. Additionally, immunohistochemistry analysis revealed that, under basal conditions, some glomeruli of the olfactory lobes showed Hsp70 immunoreactivity in an on-off manner. Both a hot environment and water deprivation increased the number of glomeruli expressing Hsp70. This marker of neuropil's activity might turn out to be a powerful tool to test whether crustacean olfactory lobes not only process olfactory information but also integrate multimodal signals.
    Neuroscience Letters 11/2008; 443(3):251-6. DOI:10.1016/j.neulet.2008.07.072 · 2.03 Impact Factor
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