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THE LONG-TERM DIETARY TREATMENT WITH 2-OXOGLUTARATE PREVENTS THE REACTIVE ASTROGLIOSIS DEVELOPMENT IN OLD GERBILS

Ushakova G.A.1, Kovalchuk Y.P.1, Kovalenko T.N.2, Osadchenko I.A.2, Skibo G.G.2, Pierzynowski S.G.3,4
1Dnepropetrovsk National University named by Oles Gonchar, Gagarin ave. 72, 49050, Dnepropetrovsk, Ukraine;
2Bogomoletz Institute of Physiology, Bogomoletz str.4, 01024, Kiev, Ukraine;
3SGPlus, Vimpelgatan 21, S-211 14 Malmo, Sweden;
4Lund University, Helgonavägen 3b, S-223 62 Lund, Sweden; Данный адрес e-mail защищен от спам-ботов, Вам необходимо включить Javascript для его просмотра.

Aging is associated with many physiological alterations such as changes in metabolism and food intake, and brain dysfunction may represent a crucial cause linking homeostatic and cognitive dysfunction. A loss of neuronal components and coupling between components of neuronal networks is characteristic of aging. Normal brain aging is associated with development of reactive astrogliosis and deficits in learning and memory. The nutrition plays an important supportive role in the management of the critically ill neurological patient, especially for old persons. Many age-dependent diseases are caused by free radical-mediated neurotoxicity induced by inhibition of mitochondrial dehydrogenases (specially, alpha-ketoglutarate dehydrogenase), followed by a decrease in neuronal mitochondrial transmembrane potential and ATP, prior to neuronal death.
The main purpose of the study was to investigate the glial reaction in the old gerbil brain after long-lasting dietary effect of 2-oxoglutarate as a food compounds.
For long-lasting feeding (during 6 month) we used 36 Mongolian gerbils, which were randomly selected into 3 groups at start of experiment: 1 - adult (6 month of age), 2 - old (18 month of age) with standard diet, 3 - old (18 month of age) with diet including  1 % Ca AKG+1 % Na2AKG. Animals were decapitated at the end of experiment under weak anesthesia, three brain areas were isolated: cerebellum, thalamus and hippocampus, which were subsequently used to obtain cytozol and cytoskeleton protein fractions. The level of S100b (calcium-binding protein) and GFAP (glial fibrillary acid protein) was determined by solid-phase competitive inhibitory ELISA. Statistical processing of results was carried out using SPSS 10.0 for Windows, the difference was considered reliable at p <0.05.
The experimental data indicate a stable level of astrocyte specific proteins in thalamus and cerebellum of gerbils aged 6 months and 2 years. A significant increase in the S100b level in old gerbils (2,1±0,6) µg/ml compared with adults (0,6±0,09) µg/ml was determined in the hippocampus indicating the development of reactive astrogliosis. Dietary treatment with 2-oxoglutarate 2 % in dry feed for 6 months inhibited the hyperactivation of astrocytes in old animals. The level of S100b protein in these animals was (1,22 ± 0,18) µg/ml. The same alteration was shown for GFAP distribution in hippocampus.
Analysis of the data indicates the absence of probable changes in metabolism of astrocyte specific proteins in thalamus and cerebellum in old gerbils, but also established a violation of integrative brain functions, information homeostasis in securing and optimizing by the hippocampus. Long-lasting dietary treatment with 2-oxoglutarate (main component of glutamate-glutamine cycle of astrocytes) prevents the development of reactive astrogliosis in the hippocampus relating to the processes of aging.

 

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