Aging and alpha-synuclein affect synaptic plasticity in the dentate gyrus.
Although intracellular accumulation of alpha-synuclein (alpha-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 alpha-syn to synaptic plasticity as well as to age-related synaptic degeneration in mice, we compared adult and aged mice overexpressing mutated (A30P) human alpha-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, alpha-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 alpha-syn exacerbates the aging process and leads to impaired synaptic plasticity.
Gureviciene
Irina
I
Department of Neurobiology, University of Kuopio, Neulaniementie 2, P.O. Box 1627, 70211, Kuopio, Finland. Irina.Gureviciene@uku.fi
Gurevicius
Kestutis
K
Tanila
Heikki
H
D000375:Aging / Q000502:physiology*; D000409:Alanine / Q000235:genetics; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001703:Biophysics; D018891:Dentate Gyrus / Q000166:cytology*; D004558:Electric Stimulation / Q000379:methods; D004924:Escape Reaction / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials / Q000235:genetics; D006801:Humans; D008124:Locomotion / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D009473:Neuronal Plasticity / Q000235:genetics / Q000502:physiology*; D019580:Perforant Pathway / Q000502:physiology; D011392:Proline / Q000235:genetics; D011930:Reaction Time / Q000235:genetics; D013569:Synapses / Q000502:physiology*; D013997:Time Factors; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism*
D051844:alpha-Synuclein; D011392:Proline; D000409:Alanine