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Development of Hippocampus-Associated Cognitive Dysfunction in Huntington’s Disease Mouse Model

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Abstract

Huntington’s disease is a hereditary, incurable, neurodegenerative disease characterized by movement disorders—progressive choreic hyperkinesia, as well as cognitive and mental disorders, including memory impairment, depression, panic attacks, obsessive compulsions, etc. According to the literature data, mild cognitive impairments begin to manifest even before the appearance of first motor symptoms. Neurodegeneration of the cortex and striatum is believed to play a major role in the development of cognitive dysfunction. At the same time, pathological changes in the hippocampus, which can also cause cognitive impairments, have been studied to a much lesser extent. In the present study, using electrophysiological experiments, morphofunctional analysis, and behavioral tests, we performed a comprehensive assessment of hippocampus-associated changes in YAC128 transgenic mice which model Huntington’s disease. The revealed disturbances in the mechanisms of synaptic plasticity and changes in the morphology of synapses in the hippocampus of YAC128 mice are progressive and occur before motor movement disorders. Thus, the obtained results support the hypothesis of the development of neurodegenerative changes in the hippocampus, which contribute to cognitive dysfunction in Huntington’s disease.

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Abbreviations

HD:

Huntington’s disease

LTP:

long-term potentiation

mHTT:

mutant huntingtin

EPSP:

excitatory postsynaptic potential

PTP:

post-tetanic potentiation

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Funding

This work was supported by the Russian Science Foundation (RSF, grant No. 19-15-00184) and the Ministry of Science and Higher Education of the Russian Federation within the World-Class Research Center (WCRC) program “Advanced digital technologies” (treaty No. 075-15-2020-934 of November 17, 2020) in the following proportion: experiments illustrated in Figs. 1, 2b–2e were supported by the RSF; the experiment in Fig. 2a was financed by the WCRC program.

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Authors and Affiliations

  1. Peter the Great St. Petersburg Polytechnic University, St. Petersburg, Russia

    N. A. Kraskovskaya, A. I. Erofeev, E. D. Grishina, S. A. Pushkareva, E. I. Gerasimov, O. L. Vlasova & I. B. Bezprozvanny

  2. Department of Physiology, UT Southwestern Medical Center at Dallas, Dallas, USA

    I. B. Bezprozvanny

Authors
  1. N. A. Kraskovskaya
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  2. A. I. Erofeev
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  3. E. D. Grishina
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  4. S. A. Pushkareva
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  5. E. I. Gerasimov
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  6. O. L. Vlasova
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  7. I. B. Bezprozvanny
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Contributions

Conceptualization and experimental design (N.A.K., A.I.E., I.B.B.); data collection (N.A.K., A.I.E., E.D.G., S.A.P., G.E.I.); data processing (N.A.K., A.I.E., E.D.G., S.A.P., G.E.I.); writing and editing the manuscript (N.A.K., A.I.E., O.L.B., I.B.B.).

Corresponding authors

Correspondence to N. A. Kraskovskaya or I. B. Bezprozvanny.

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CONFLICT OF INTEREST

The authors declare that they have neither evident nor potential conflict of interest related to the publication of this article.

Additional information

Translated by A. Polyanovsky

Russian Text © The Author(s), 2021, published in Rossiiskii Fiziologicheskii Zhurnal imeni I.M. Sechenova, 2021, Vol. 107, No. 12, pp. 1490–1504https://doi.org/10.31857/S0869813921120050.

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Kraskovskaya, N.A., Erofeev, A.I., Grishina, E.D. et al. Development of Hippocampus-Associated Cognitive Dysfunction in Huntington’s Disease Mouse Model. J Evol Biochem Phys 57, 1449–1460 (2021). https://doi.org/10.1134/S0022093021060211

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