Modulators of endogenous cannabinoid system аs neuroprotectors

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Abstract

The neuroprotective action of endocannabinoid N-arachidonoyldopamine (AA-DA) in the model of apoptosis induced in cultured rat cerebellar granule neurons by K+ deprivation was investigated. The efficacy of simultaneous application of AA-DA with fatty acid amide hydrolase inhibitor N-eicosapentaenoyldopamine (EPA-5HT) was also evaluated. It was shown that AA-DA dose-dependently protects neurons, with maximal effect of 65% survived cells observed at concentration 10 μM. The use of submaximal concentration (5 μM) of AA-DA in combination with EPA-5HT (10 μM) led to significant enhancement of neuroprotection. The value of cell survival for the combination exceeded such values for AA-DA alone in concentration of 5 and 10 μM, increasing the neuronal survival up to 78%. It may be concluded that such combination allows to reduce efficient concentration of neuroprotector and to diminish its possible side effects. Thus, the simultaneous application of endocannabinoid system modulators such as cannabinoid receptor agonists and inhibitors of endocannabinoid hydrolysis appears to be effective approach for neural cells protection.

 

About the authors

Elizaveta E. Genrikhs

Research Center of Neurology

Email: mbobr@mail.ru
Россия, Moscow

M. Yu. Bobrov

Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Medical Sciences

Email: mbobr@mail.ru
Россия, Moscow

E. L. Andrianova

Research Center of Neurology

Email: mbobr@mail.ru
Россия, Moscow

N. M. Gretskaya

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences

Email: mbobr@mail.ru
Россия, Moscow

A. A. Lyzhin

Research Center of Neurology

Email: mbobr@mail.ru
Россия, Moscow

A. V. Blazhenova

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences

Email: mbobr@mail.ru
Россия, Moscow

L. E. Frumkina

Research Center of Neurology, Russian Academy of Medical Sciences

Email: mbobr@mail.ru
Россия, Moscow

V. V. Bezuglov

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences

Email: mbobr@mail.ru
Россия, Moscow

Leonid G. Khaspekov

Research Center of Neurology

Author for correspondence.
Email: mbobr@mail.ru
Россия, Moscow

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Copyright (c) 2010 Genrikhs E.E., Bobrov M.Y., Andrianova E.L., Gretskaya N.M., Lyzhin A.A., Blazhenova A.V., Frumkina L.E., Bezuglov V.V., Khaspekov L.G.

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