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The effects of α-synuclein oligomers on neurogenesis in the hippocampus and the behavior of aged mice

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Abstract

We studied the effects of intranasal administration of oligomeric forms of the α-synuclein protein, which plays an important role in the pathogenesis in a group of chronic neurodegenerative diseases, that is, synucleinopathies. Neurogenesis in the hippocampus, the number of dopaminergic neurons in the substantia nigra, locomotor and orienting-exploratory activity, learning and memory, and the emotional state were studied in aged animals. Twelve-month-old male C57Bl/6 mice were used for the experiments. The solution of oligomers of α-synuclein was administered daily to mice for 14 days. The behavioral testing included the open-field test, novel-object recognition, passive avoidance conditioning, and the elevated plus-maze. Proliferating cells, immature neurons, and dopaminergic neurons were detected using immunohistochemical staining with antibodies to the bromodeoxyuridine, doublecortin, and tyrosine hydroxylase markers. We found that α-synuclein oligomers induced a significant increase in the number of proliferating cells and immature neurons in the hippocampal dentate gyrus and a decrease in the number of dopaminergic neurons in the substantia nigra pars compacta. The treated mice exhibited decreased locomotor and orienting-exploratory activities, impaired formation and retrieval of episodic memory, and increased anxiety. Our data show that the non-motor behavioral effects of α-synuclein oligomers may be related to impairments in hippocampal neurogenesis and may be considered as experimental evidence of the involvement of postnatal neurogenesis in the development of synucleinopathies.

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Authors and Affiliations

  1. Anokhin Institute of Normal Physiology, Moscow, Russia

    V. V. Sherstnev, A. V. Kedrov, O. A. Solov’eva, M. A. Gruden’, E. V. Konovalova, I. A. Kalinin & A. T. Proshin

  2. ul. Baltiiskaya 8, Moscow, 125315, Russia

    V. V. Sherstnev

Authors
  1. V. V. Sherstnev
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  2. A. V. Kedrov
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  3. O. A. Solov’eva
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  4. M. A. Gruden’
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  5. E. V. Konovalova
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  6. I. A. Kalinin
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  7. A. T. Proshin
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Correspondence to V. V. Sherstnev.

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Original Russian Text © V.V. Sherstnev, A.V. Kedrov, O.A. Solov’eva, M.A. Gruden’, E.V. Konovalova, I.A. Kalinin, A.T. Proshin, 2017, published in Neirokhimiya, 2017, Vol. 34, No. 4, pp. 281–289.

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Sherstnev, V.V., Kedrov, A.V., Solov’eva, O.A. et al. The effects of α-synuclein oligomers on neurogenesis in the hippocampus and the behavior of aged mice. Neurochem. J. 11, 282–289 (2017). https://doi.org/10.1134/S1819712417040092

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