Exogenous protein Hsp70/Hsc70 can penetrate into brain structures and attenuate the severity of chemically‐induced seizures

Abstract

J. Neurochem. (2010) 115, 1035–1044. Abstract 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.

Overexpression of Hsp27 ameliorates symptoms of Alzheimer's disease in APP/PS1 mice

“…This is in accordance with earlier findings of others who demonstrated that seizure susceptibility is increased in AD model mice (Westmark et al 2008;Vogt et al 2009), and heat shock proteins can moderate chemically induced seizures (Akbar et al 2003;Ekimova et al 2010). LTP, a cellular correlate of learning and memory (Bliss and Colingridge 1993), was also investigated on hippocampal slices.…”

Exogenous Hsp70 delays senescence and improves cognitive function in aging mice

“…One mechanism underlying our results may be the neuroprotective effect of Hsp70 on synaptic machinery. An investigation of recombinant Hsp70 localization after intracerebroventricular injection found the protein in neurons and colocalized with synaptophysin (39). In the present study, total neuron density was significantly higher in the cortex and CA1-CA2 areas of the hippocampus in eHsp70 treated mouse brain.…”

Hsp70 chaperone-based gel composition as a novel immunotherapeutic anti-tumor tool

“…Given that Hsp70 can penetrate inside cells or tissues (Guzhova et al 2001;Ekimova et al 2010), we suggested that the protein may cross the skin layers and migrate to a malignant tissue. To verify this suggestion, the gelcontaining Hsp70 was assembled, and the transport of the chaperone was analyzed with the aid of histochemistry.…”