Assessment of the effects of cellular therapy on reproduction of the conditioned passive avoidance reflex in rats with quinoline-induced model of Huntington’s disease

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Introduction. The model involving injection of quinolinic acid (QA) into the rat striatum simulates many clinical and morphological characteristics of Huntington’s disease (HD). Searching for effective treatment methods is rather topical because of the fatality of HD. One of such methods is to create a neuroprotective environment to slow down the current degenerative process and/or replace dead neurons. In particular, this can be performed by transplantation of cells capable of undergoing neuronal differentiation and integration into the proper structural and functional brain networks.

Objective. To assess effectiveness and safety of transplantation of neural progenitors differentiated from induced pluripotent stem cells (iPSCs) harvested from a healthy donor into the striatum with QA-induced model of HD.

Materials and methods. The effects of neurotransplantation on reproduction of the conditioned passive avoidance reflex were studied in rats with the model of HD induced by injection of QA into the caudate nuclei of the striatum. In the study group (n=8), human neural progenitors (1×106 per 10 µl of normal saline unilaterally, on the injured side) derived from iPSCs harvested from a healthy donor were injected into the caudate nuclei as the transplanted material; normal saline was injected in the control group. The conditioned passive avoidance responses were tested using the ShutАvoid 1.8.03 software on a Harvard apparatus (Panlab, Spain).

Results. When testing the reproduction of the passive avoidance responses, we found that injection of QA into the caudate nuclei of the rat brain reliably reduced the conditioned responses. Neurotransplantation of neural progenitors derived from iPSCs had a clear therapeutic effect and reinforced the passive avoidance reflex. During the entire testing period (7 days after exposure to the pain stimulus), the experimental animals either did not visit the dark compartment at all or visited it with a long latency period.

Conclusions. Experimental neurotransplantation using iPSC derivatives allowance to improve storage of trace memory in rats with QA-induced model of HD, which contributes to correction of cognitive impairments caused by administration of the neurotoxin.

About the authors

Alla V. Stavrovskaya

Research Center of Neurology

Author for correspondence.
Russian Federation, Moscow

Ekaterina V. Novosadova

Institute of Molecular Genetics of RAS

Russian Federation, Moscow

Nina G. Yamshchikova

Research Center of Neurology

Russian Federation, Moscow

Artem S. Olshansky

Research Center of Neurology

Russian Federation, Moscow

Anastasiya S. Gushchina

Research Center of Neurology

Russian Federation, Moscow

Eugeniya V. Konovalova

Research Center of Neurology

Russian Federation, Moscow

Igor' A. Grivennikov

Institute of Molecular Genetics of RAS

Russian Federation, Moscow

Sergey N. Illarioshkin

Research Center of Neurology

ORCID iD: 0000-0002-2704-6282

D. Sci. (Med.), Prof., Corr. Member of the Russian Academy of Sciences, Deputy Director, Head, Department for brain research

Russian Federation, Moscow


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Copyright (c) 2017 Stavrovskaya A.V., Novosadova E.V., Yamshchikova N.G., Ol’shansky A.S., Gushchina A.S., Konovalova E.V., Grivennikov I.A., Illarioshkin S.N.

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