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

Authors

  • Irina V. Ekimova,

    1. Laboratory of Comparative Thermophysiology, I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry Russian Academy of Sciences, St. Petersburg, Russia
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  • Larisa E. Nitsinskaya,

    1. Laboratory of Comparative Thermophysiology, I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry Russian Academy of Sciences, St. Petersburg, Russia
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  • Irina V. Romanova,

    1. Laboratory of Comparative Somnology and Neuroendocrinology, I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry Russian Academy of Sciences, St. Petersburg, Russia
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  • Yuri F. Pastukhov,

    1. Laboratory of Comparative Thermophysiology, I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry Russian Academy of Sciences, St. Petersburg, Russia
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  • Boris A. Margulis,

    1. Cell Protection Mechanisms Laboratory, Institute of Cytology Russian Academy of Sciences, St. Petersburg, Russia
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  • Irina V. Guzhova

    1. Cell Protection Mechanisms Laboratory, Institute of Cytology Russian Academy of Sciences, St. Petersburg, Russia
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Address correspondence and reprint requests to Irina V. Guzhova, Cell Protection Mechanisms Laboratory, Institute of Cytology Russian Academy of Sciences, Tikhoretsky pr., 4 St. Petersburg, Russia, 194064. E-mail: guzhova@mail.cytspb.rssi.ru

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.

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