INHIBITION OF NEUROINFLAMMATION REDUCES DEGENERATION OF DOPAMINERGIC NEURONS IN THE SUBSTANTIANIGRA INDUCED BY OVEREXPRESSION OF THE RECOMBINANT ALPHASYNUCLEINGENE
We investigated the effect of overexpression of alpha-synuclein in the dopaminergic neurons on neurodegeneration and proinflammatory activation of microglial cells in the substantia nigra to test hypotheses about the relationship of neuroinflammation and neurodegeneration. The degree of neuroinflammation influence on neurodegeneration judged by the administration of corticosterone to rats with rAAV human alpha-synuclein. It has been found that the introduction of the vector dramatically reduces the number of dopaminergic neurons (-86,5+16,8%), while corticosterone injection significantly increased the number of surviving dopaminergic neurons in rats with rAAV human alpha-synuclein (+35,7+12,4%). Immunohistochemical study showed a increase in the expression of MHC II and IL-1 and the severity of gliosis. The findings suggest that there is neurodegenerative effect of elevated levels of endogenous alpha-synuclein, and its pro-inflammatory effect on microglia activation which, in turn, increases the intensity of neurodegeneration.