Accumulation of formaldehyde causes motor deficits in an in vivo model of hindlimb unloading.

Communications biology 2021 Aug 19

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During duration spaceflight, or after their return to earth, astronauts have often suffered from gait instability and cerebellar ataxia. Here, we use a mouse model of hindlimb unloading (HU) to explore a mechanism of how reduced hindlimb burden may contribute to motor deficits. The results showed that these mice which have experienced HU for 2 weeks exhibit a rapid accumulation of formaldehyde in the gastrocnemius muscle and fastigial nucleus of cerebellum. The activation of semicarbazide-sensitive amine oxidase and sarcosine dehydrogenase induced by HU-stress contributed to formaldehyde generation and loss of the abilities to maintain balance and coordinate motor activities. Further, knockout of formaldehyde dehydrogenase (FDH-/-) in mice caused formaldehyde accumulation in the muscle and cerebellum that was associated with motor deficits. Remarkably, formaldehyde injection into the gastrocnemius muscle led to gait instability; especially, microinfusion of formaldehyde into the fastigial nucleus directly induced the same symptoms as HU-induced acute ataxia. Hence, excessive formaldehyde damages motor functions of the muscle and cerebellum. © 2021. The Author(s).

Citation

Dandan Yao, Qingyuan He, Shangying Bai, Hang Zhao, Jun Yang, Dehua Cui, Yan Yu, Xuechao Fei, Yufei Mei, Ye Cheng, Shi Yan, Nayan Huang, Yalan Di, Xianjie Cai, Rui Wang, Yajuan Gao, Fangxiao Cheng, Shengjie Zhao, Xu Yang, Xiang Cai, Hongbin Han, Jihui Lyu, Zhiqian Tong. Accumulation of formaldehyde causes motor deficits in an in vivo model of hindlimb unloading. Communications biology. 2021 Aug 19;4(1):933