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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<jats:sup>-\/-<\/jats:sup>) 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.<\/jats:p>","DOI":"10.1038\/s42003-021-02448-9","type":"journal-article","created":{"date-parts":[[2021,8,19]],"date-time":"2021-08-19T16:10:21Z","timestamp":1629389421000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Accumulation of formaldehyde causes motor deficits in an in vivo model of hindlimb unloading"],"prefix":"10.1038","volume":"4","author":[{"given":"Dandan","family":"Yao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingyuan","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shangying","family":"Bai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hang","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dehua","family":"Cui","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuechao","family":"Fei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yufei","family":"Mei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ye","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shi","family":"Yan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nayan","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yalan","family":"Di","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xianjie","family":"Cai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rui","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yajuan","family":"Gao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fangxiao","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shengjie","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8015-6299","authenticated-orcid":false,"given":"Xu","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiang","family":"Cai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongbin","family":"Han","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1035-6943","authenticated-orcid":false,"given":"Jihui","family":"Lyu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0511-0386","authenticated-orcid":false,"given":"Zhiqian","family":"Tong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,8,19]]},"reference":[{"key":"2448_CR1","first-page":"3","volume":"40","author":"AI Grigor\u2019ev","year":"2006","unstructured":"Grigor\u2019ev, A. 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