» Articles » PMID: 34413463

Accumulation of Formaldehyde Causes Motor Deficits in an in Vivo Model of Hindlimb Unloading

Abstract

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.

Citing Articles

Formaldehyde initiates memory and motor impairments under weightlessness condition.

Mei T, Chen Y, Gao Y, Zhao H, Lyu X, Lin J NPJ Microgravity. 2024; 10(1):100.

PMID: 39468074 PMC: 11519943. DOI: 10.1038/s41526-024-00441-0.


Opposite Roles of Co-enzyme Q10 and Formaldehyde in Neurodegenerative Diseases.

Xu J, Jin X, Ye Z, Wang D, Zhao H, Tong Z Am J Alzheimers Dis Other Demen. 2022; 37:15333175221143274.

PMID: 36455136 PMC: 10624093. DOI: 10.1177/15333175221143274.


Acute high-altitude hypoxia exposure causes neurological deficits via formaldehyde accumulation.

Wang X, Sun H, Cui L, Wang X, Ren C, Tong Z CNS Neurosci Ther. 2022; 28(8):1183-1194.

PMID: 35582960 PMC: 9253739. DOI: 10.1111/cns.13849.

References
1.
Grigorev A . [Aerospace biology and medicine, aerospace biotechnology and astrobiology Russian Federation government program]. Aviakosm Ekolog Med. 2006; 40(1):3-4. View

2.
Black F, Paloski W, Reschke M, Igarashi M, Guedry F, Anderson D . Disruption of postural readaptation by inertial stimuli following space flight. J Vestib Res. 1999; 9(5):369-78. View

3.
Fujii M, PATTEN B . Neurology of microgravity and space travel. Neurol Clin. 1992; 10(4):999-1013. View

4.
Paloski W . Vestibulospinal adaptation to microgravity. Otolaryngol Head Neck Surg. 1998; 118(3 Pt 2):S39-44. DOI: 10.1016/S0194-59989870008-7. View

5.
Paloski W, Reschke M, Black F, Doxey D, Harm D . Recovery of postural equilibrium control following spaceflight. Ann N Y Acad Sci. 1992; 656:747-54. DOI: 10.1111/j.1749-6632.1992.tb25253.x. View