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Aim  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.    Methods  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.    Key Results  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.    Conclusions  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.

Early manifestation of depressive‐like behavior in transgenic mice that express dementia with Lewy body‐linked mutant β‐synuclein