Gureviciene Irina, Gurevicius Kestutis, Tanila Heikki
Department of Neurobiology, University of Kuopio, Neulaniementie 2, P.O. Box 1627, 70211, Kuopio, Finland.
J Neural Transm (Vienna). 2009 Jan;116(1):13-22. doi: 10.1007/s00702-008-0149-x. Epub 2008 Nov 11.
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.
尽管α-突触核蛋白（α-syn）在细胞内的积累是帕金森病、路易体痴呆症和阿尔茨海默病的特征性病理变化，但这种突触前蛋白的正常功能仍然未知。为了评估α-syn对小鼠突触可塑性以及与年龄相关的突触退化的影响，我们使用行为测试和齿状回的电生理测量方法，将过表达突变型（A30P）人α-syn的成年和老年小鼠与其非转基因同窝小鼠进行了比较。我们发现老年小鼠的穿通通路-齿状颗粒细胞突触的基础突触传递和双脉冲易化作用降低。此外，老年A30P小鼠而非老年野生型小鼠中的α-syn积累导致在通常诱导长时程增强的刺激方案后突触传递的长时程抑制。这些发现表明，突变型α-syn的过表达会加剧衰老过程并导致突触可塑性受损。
