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Hippocampal Neurogenesis, Dopaminergic Neurons of the Substantia Nigra, and Behavior after Intranasal Administration of Native α-Synuclein Protein to Ageing Mice

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Abstract—We studied the effects of intranasal administration of native α-synuclein, whose hyperproduction and misfolding are the key link in the pathogenesis of Parkinson’s disease and other age-related neurodegenerative diseases, on hippocampal neurogenesis, the number of dopaminergic neurons in the substantia nigra, locomotor activity, learning, memory, and anxiety level in ageing animals. The experiments were performed with 12-month-old C57BL/6 male mice which were treated for 14 days with a solution of recombinant native α-synuclein or physiological saline once every 24 hours. To evaluate behavioral indices, the following tests were used: open field, novel object recognition, conditioned passive avoidance response, and elevated plus maze. Proliferating cells, immature neurons, and dopaminergic nerve cells were immunohistochemically detected using antibodies against bromodeoxyuridine, doublecortin, and tyrosine hydroxylase. It was demonstrated that α-synuclein causes a considerable increase in the number of proliferating cells and a decrease in the number of immature neurons in the dentate gyrus the hippocampus, as well as a decrease in the density of dopaminergic neurons in the substantia nigra pars compacta. Mice that received native α-synuclein demonstrated lower locomotion speed, impairments in long-term associative memory, and changes in anxiety-like behavior. We compared the obtained data with the previous results on the effects of α-synuclein oligomers and fibrils under similar experimental protocols. The data are viewed as experimental evidence of the impairment of postnatal neurogenesis during the development of synucleinopathies and support the notion that different α-synuclein conformations cause the development of different neurodegenerative diseases.

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ACKNOWLEDGEMENTS

The authors express gratitude to Professor Ludmilla Morozova-Roche, Department of Medical Biochemistry and Biophysics, Umeå University, Sweden, for providing native α-synuclein protein.

Funding

The work was supported by the Russian Foundation for Basic Research, project no. 16-04-00661а.

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Authors and Affiliations

  1. Anokhin Institute of Normal Physiology, ul. Baltiiskaya 8, 125315, Moscow, Russia

    V. V. Sherstnev, O. A. Solov’eva, M. A. Gruden’, A. M. Ratmirov & E. V. Konovalova

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  1. V. V. Sherstnev
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  2. O. A. Solov’eva
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  3. M. A. Gruden’
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  4. A. M. Ratmirov
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  5. E. V. Konovalova
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Correspondence to V. V. Sherstnev.

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Conflict of interests. The authors declare no conflicts of interest.

Ethical approval. All the experiments with animals were conducted in compliance with ethical standards and rules on the use of experimental animals in scientific research contained in Directive 2010/63/EU and EU Council on animals used in research, of 22.09.2010, and approved by the Bioethics Commission of the FSBSI “P.K. Anokhin Institute of Normal Physiology.”

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Sherstnev, V.V., Solov’eva, O.A., Gruden’, M.A. et al. Hippocampal Neurogenesis, Dopaminergic Neurons of the Substantia Nigra, and Behavior after Intranasal Administration of Native α-Synuclein Protein to Ageing Mice. Neurochem. J. 15, 71–78 (2021). https://doi.org/10.1134/S181971242101013X

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  • DOI: https://doi.org/10.1134/S181971242101013X

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