Fujita Masayo, Hagino Yoko, Takamatsu Yukio, Shimizu Yuka, Takamatsu Yoshiki, Ikeda Kazutaka, Hashimoto Makoto
Addictive Substance Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
Center for Basic Technology Research, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
Neuropsychopharmacol Rep. 2018 Jun;38(2):95-97. doi: 10.1002/npr2.12009. Epub 2018 Mar 7.
We previously generated transgenic (Tg) mice that expressed P123H β-synuclein (βS), a dementia with Lewy body-linked mutant βS. Notably, these mice recapitulated neurodegenerative features of Lewy body disease, reflected by motor dysfunction, greater protein aggregation, and memory impairment. Since recent studies suggested that non-motor symptoms, such as depression, might be manifested in the prodromal stage of Lewy body disease, the main objective of the present study was to investigate the early expression of behavior in P123H βS Tg mice.
Nest building, locomotor activity, and depressive-like behavior were assessed using 6- to 10-month-old male and female P123H βS Tg and wildtype mice.
P123H βS Tg mice exhibited hyperlocomotor activity in a novel environment, a decrease in mobility time in the tail suspension test, and impairments in nest building.
Importantly, these non-motor behaviors were manifested before the onset of motor dysfunction, suggesting that P123H βS Tg mice could be a valid model for investigating the early phase of Lewy body disease.
我们之前培育出了表达P123Hβ-突触核蛋白（βS）的转基因（Tg）小鼠，P123Hβ-突触核蛋白是一种与路易体痴呆相关的突变βS。值得注意的是，这些小鼠重现了路易体病的神经退行性特征，表现为运动功能障碍、更多的蛋白质聚集和记忆损伤。由于最近的研究表明，诸如抑郁等非运动症状可能在路易体病的前驱期出现，本研究的主要目的是调查P123HβS转基因小鼠行为的早期表现。
使用6至10月龄的雄性和雌性P123HβS转基因小鼠和野生型小鼠评估筑巢、运动活动和抑郁样行为。
P123HβS转基因小鼠在新环境中表现出运动活动亢进，在悬尾试验中活动时间减少，筑巢能力受损。
重要的是，这些非运动行为在运动功能障碍出现之前就已表现出来，这表明P123HβS转基因小鼠可能是研究路易体病早期阶段的有效模型。
