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Assessment of the Effects of Cell Therapy on Reproduction of the Conditioned Passive Avoidance Reflex in Rats with Quinoline-Induced Model of Huntington’s Disease

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Abstract

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 important 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 neuronal differentiation and integration into the proper structural and functional brain networks. Objective: To assess effectiveness and safety of transplantation of neural precursor cells differentiated from induced pluripotent stem cells (iPSCs) taken from a healthy donor into the striatum of rats 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 HD model 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 taken from a healthy donor were injected into the caudate nuclei as the transplanted material; normal saline was injected to the control group. The conditioned passive avoidance responses were tested with 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 allowed 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.

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Authors and Affiliations

  1. Research Center of Neurology, 125367, Moscow, Russia

    A. V. Stavrovskaya, N. G. Yamshchikova, A. S. Ol’shansky, A. S. Gushchina, E. V. Konovalova & S. N. Illarioshkin

  2. Institute of Molecular Genetics RAS, Moscow, Russia

    E. V. Novosadova & I. A. Grivennikov

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  1. A. V. Stavrovskaya
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  2. E. V. Novosadova
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  4. A. S. Ol’shansky
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Correspondence to A. V. Stavrovskaya.

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Stavrovskaya, A.V., Novosadova, E.V., Yamshchikova, N.G. et al. Assessment of the Effects of Cell Therapy on Reproduction of the Conditioned Passive Avoidance Reflex in Rats with Quinoline-Induced Model of Huntington’s Disease. Hum Physiol 44, 901–905 (2018). https://doi.org/10.1134/S036211971808011X

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