Seipin Deficiency Impairs Motor Coordination in Mice by Compromising Spinal Cord Myelination.

Abstract

The integrity of the myelin sheath of the spinal cord (SC) is essential for motor coordination. Seipin is an endoplasmic reticulum transmembrane protein highly expressed in adipose tissue and motor neurons in the SC. It was reported Seipin deficiency induced lipid dysregulation and neurobehavioral deficits, but the underlying mechanism, especially in SC, remains to be elucidated. In present study, we found that Seipin and myelin basic protein (MBP) increased synchronously in SC of developmental stage of mice. Demyelination impaired motor coordination as well as MBP and Seipin expression, which were alleviated by remyelination. Moreover, Seipin deficiency impaired motor coordination of mice, accompanied by hypomyelination in spinal cord. Mechanistically, we further demonstrated that myelin content as labeled by Fluormyelin, myelin basic protein (MBP) was down-regulated by Seipin deficiency. Seipin deficiency led to reduction of myelin-forming oligodendrocytes (OLs) density in spinal cord. Notably, administration of rosiglitazone (RG), a classic PPARγ activator, successfully restored the phenotypes manifested by Seipin deficiency including reduced OLs density, hypomyelination, as well as motor dyscoordination. In summary, present study revealed that Seipin deficiency disrupted motor coordination by compromising myelination in SC, and RG treatment could rescue the phenotypes. This study throws light on the mechanism underlying Seipin deficiency associated disorders and paves ways for developing therapeutics toward those diseases.