Effect Of Transmembrane Protein 108 On Differentiation And Maturation Of Oligodendrocytes

In the central nervous system,oligodendrocytes are derived from oligodendrocyte progenitors.Mature oligodendrocytes are able to wrap axons and form myelin sheath,allowing for jump-type conduction of action potential possible.Pathological changes of oligodendrocytes are in various neurological diseases,including Multiple sclerosis,Schizophrenia and Alzheimer’s disease.Transmembrane protein 108(Tmem108)is located on human chromosome 3Q21.Previous studies have identified Tmem108 as a susceptibility gene for a variety of neurological disorders,including Schizophrenia,Bipolar disorder and Major depression diseases.In previous studies,we found that Tmem108 protein was highly expressed during the critical period of myelin sheath development in the prefrontal cortex of mice,and was mainly expressed in newly formed oligodendrocytes.In the prefrontal cortex of systemic Tmem108 knockout mice,the number of mature oligodendrocytes and myelin sheath expression decreased.In addition,whole-body knockout Tmem108 mice had impaired cognitive function.To further explore the effect of Tmem108 on oligodendrocyte,we cultured oligodendrocyte progenitor cells in vitro and used Tmem108 small interfering plasmid to study the effect of Tmem108 knockdown on the proliferation,differentiation and maturation of oligodendrocyte.The results showed that Tmem108 knockdown did not affect the proliferation of oligodendrocyte progenitor cells,but reduced the number of mature oligodendrocyte cells after induction.We further constructed a Cre-dependent recombinant adeno-associated virus that interferes with sh RNA of Tmem108 and injected it stereologically into the prefrontal lobe of PDGFRα-cre mice to knock down Tmem108 expression during oligodendrocyte development and maturation.After stable virus expression,oligodendrocyte numbers and myelin sheath expression levels in prefrontal lobes of PDGFRα-cre mice,as well as behavioral and cognitive functions were measured.The results showed that specific knockdown of Tmem108 resulted in a decrease in the number of mature oligodendrocytes and myelin sheath expression in the prefrontal cortex of mice,and impaired cognitive function.These results suggest that transmembrane protein 108 affects myelin sheath development and cognitive function of mice by influencing oligodendrocyte maturation.Reduced expression of Tmem108 inhibits oligodendrocyte maturation and myelin sheath development,and is associated with cognitive impairment such as decreased learning ability,memory loss and social ability.This work further demonstrates the role of transmembrane protein 108 in the differentiation and maturation of oligodendrocytes,providing a research strategy for the treatment of neuropathologically altered oligodendrocytes,and providing a theoretical basis for the pathogenesis of Schizophrenia and Bipolar disorder.