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Aging and α-synuclein affect synaptic plasticity in the dentate gyrus

  • Basic Neurosciences, Genetics and Immunology - Original Article
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Abstract

Although intracellular accumulation of α-synuclein (α-syn) is a characteristic pathological change in Parkinson’s disease, Lewy body dementia and Alzheimer’s disease, the normal function of this presynaptic protein is still unknown. To assess the contribution of α-syn to synaptic plasticity as well as to age-related synaptic degeneration in mice, we compared adult and aged mice overexpressing mutated (A30P) human α-syn with their nontransgenic littermates using behavioral tests and electrophysiological measures in the dentate gyrus. We found decreased basal synaptic transmission and paired-pulse facilitation in the perforant path-dentate granule cell synapses of aged mice. In addition, α-syn accumulation in aged A30P mice but not in aged wild-type mice led to long-term depression of synaptic transmission after a stimulation protocol that normally induces long-term potentiation. These findings suggest that overexpression of mutated α-syn exacerbates the aging process and leads to impaired synaptic plasticity.

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Acknowledgments

We thank S. Vepsäläinen and P. Räsänen (Department of Neuroscience and Neurology, University of Kuopio) for technical assistance in mouse genotyping and H. Iivonen (Department of Neurobiology, University of Kuopio) for technical assistance in water maze testing. This study was supported by the Finnish Cultural Foundation, the Northern-Savonia Foundation, and the Academy of Finland.

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Authors and Affiliations

  1. Department of Neurobiology, A. I. Virtanen Institute for Molecular Science, University of Kuopio, Neulaniementie 2, P.O. Box 1627, 70211, Kuopio, Finland

    Irina Gureviciene, Kestutis Gurevicius & Heikki Tanila

  2. Department of Neurology, Kuopio University Hospital, P.O. Box 1777, 70211, Kuopio, Finland

    Heikki Tanila

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  1. Irina Gureviciene
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  2. Kestutis Gurevicius
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  3. Heikki Tanila
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Correspondence to Irina Gureviciene.

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Gureviciene, I., Gurevicius, K. & Tanila, H. Aging and α-synuclein affect synaptic plasticity in the dentate gyrus. J Neural Transm 116, 13–22 (2009). https://doi.org/10.1007/s00702-008-0149-x

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  • DOI: https://doi.org/10.1007/s00702-008-0149-x

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