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

作者：Gureviciene Irina^*; Gurevicius Kestutis; Tanila Heikki

来源：Journal of Neural Transmission, 2009, 116(1): 13-22.

DOI：10.1007/s00702-008-0149-x

• alpha-Synuclein
• Dentate gyrus
• Perforant pathway
• Paired-pulse facilitation
• Transgenic

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.

• 出版日期2009-1