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

• Published in: Journal of neurochemistry Vol. 115; no. 4; pp. 1035 - 1044
• Main Authors: Ekimova, Irina V, Nitsinskaya, Larisa E, Romanova, Irina V, Pastukhov, Yuri F, Margulis, Boris A, Guzhova, Irina V
• Format: Journal Article
• Language: English; Russian
• Published: Oxford, UK Blackwell Publishing Ltd 01.11.2010; Wiley-Blackwell
• Subjects: Animals; Anticonvulsants; Anticonvulsants - metabolism; Anticonvulsants - therapeutic use; Brain; Brain - drug effects; Brain - metabolism; Brain - physiopathology; Cattle; Central nervous system; Chaperones; chemically‐induced seizures; Convulsions & seizures; Enzymes; Epilepsy; g-Aminobutyric acid; GAD67; Glutamic acid receptors (ionotropic); Heat shock proteins; HSC70 Heat-Shock Proteins - physiology; HSC70 Heat-Shock Proteins - therapeutic use; Hsp70; HSP70 Heat-Shock Proteins - physiology; HSP70 Heat-Shock Proteins - therapeutic use; Hsp70 protein; Humans; Immunoprecipitation; Male; Microinjection; N-Methyl-D-aspartic acid receptors; N-Methylaspartate - toxicity; Neurochemistry; Neurons; Neuroprotection; Neurotransmission; Pentylenetetrazole; Pentylenetetrazole - toxicity; Prospective Studies; Protein Transport - drug effects; Protein Transport - physiology; rat; Rats; Rats, Wistar; Recombinant Proteins - pharmacology; Recombinant Proteins - therapeutic use; Rodents; Seizures; Seizures - chemically induced; Seizures - metabolism; Seizures - physiopathology; Seizures - prevention & control; Severity of Illness Index; Shock; Synaptophysin
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2010.06989.x

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.