Experimental parkinsonism in modeling striatal astrocyte damage

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Introduction. Astrocyte dysfunction is typical for many CNS pathologies, yet few experimental models of selective astrocyte damage, which would enable a fuller understanding of the role of astrocytes in the pathogenesis of neurodegenerative disorders, exist.

Study aim — to characterize the morphological brain changes with the administration of α-aminoadipic acid (L-AA), a glial toxin, into the rat striatum and to assess the effect of astrocyte dysfunction on motor activity in animals.

Materials and methods. Astrocyte damage was achieved by administering L-AA (100 μg in 5 μl) into the rats’ right striatum; the same volume of phosphate-buffered saline was injected into the left hemisphere as a control. On the third day after L-AA administration, motor impairment was assessed with normal and reduced dopaminergic neurotransmission; the latter was achieved with administration of the α-methyl-p-tyrosine, a tyrosine hydroxylase inhibitor. The immunohistochemical studies included assays for glial fibrillary acidic protein (GFAP), neuronal nuclear antigen (NeuN), and tyrosine hydroxylase.

Results. When dopamine synthesis was inhibited, damage to the striatal astrocytes, which was confirmed by immunohistochemistry, caused a reduction in motor activity in the open field test and an increase in the number of errors in the beam walking test. When dopaminergic transmission was reduced through the inhibition of tyrosine hydroxylase by α-methyl-p-tyrosine, the motor disturbances caused by astrocyte damage sustained and worsened.

Conclusion. The obtained data indicate the regulatory role of astroglia in the nigrostriatal system and emphasize the possible contribution of glial dysfunction to the motor disturbances in Parkinson’s disease.

About the authors

Alla V. Stavrovskaya

Research Center of Neurology

Author for correspondence.
Email: alla_stav@mail.ru
Russian Federation, Moscow

Dmitry N. Voronkov

Research Center of Neurology

Email: alla_stav@mail.ru
Russian Federation, Moscow

Artyem S. Ol’shansky

Research Center of Neurology

Email: alla_stav@mail.ru
Russian Federation, Moscow

Anastasiya S. Gushchina

Research Center of Neurology

Email: alla_stav@mail.ru
Russian Federation, Moscow

Nina G. Yamshchikova

Research Center of Neurology

Email: alla_stav@mail.ru
Russian Federation, Moscow


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Supplementary files

Supplementary Files

Copyright (c) 2019 Stavrovskaya A.V., Voronkov D.N., Ol’shansky A.S., Gushchina A.S., Yamshchikova N.G.

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