Masayo Fujita1, Yoko Hagino1, Yukio Takamatsu2, Yuka Shimizu3, Yoshiki Takamatsu3, Kazutaka Ikeda1, Makoto Hashimoto3. 1. Addictive Substance Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan. 2. Center for Basic Technology Research, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan. 3. Laboratory of Parkinson's Disease, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
Abstract
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.
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 asdepression, 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.
Authors: Julia Marschallinger; Barbara Altendorfer; Edward Rockenstein; Miriam Holztrattner; Julia Garnweidner-Raith; Nadine Pillichshammer; Iris Leister; Birgit Hutter-Paier; Katharina Strempfl; Michael S Unger; Mansoor Chishty; Thomas Felder; Mary Johnson; Johannes Attems; Eliezer Masliah; Ludwig Aigner Journal: Neurotherapeutics Date: 2020-07 Impact factor: 6.088