title: Chronic stress regulates NG2⁺ cell maturation and myelination in the prefrontal cortex through induction of death receptor 6.
abstract: Chronic stress significantly affects neuron morphometry and function in the prefrontal cortex, a brain region controlling cognition and emotion. However, whether and how chronic stress regulates the maturation of NG2-expressing oligodendrocyte precursor cell (NG2(+) cell) and the importance of these changes remained unknown. Here, we report that exposing adult mice to chronic stress results in NG2(+) cell atrophy and myelination arrested in the medial prefrontal cortex (mPFC), and impaired mPFC-dependent functions. These alterations, are phenocopied by overexpression of death receptor 6 (DR6) in NG2(+) cell. Conversely, selectively silencing of DR6 in the NG2(+) cell can partly rescue NG2(+) cell atrophy and cognitive deficiency caused by chronic stress. We further demonstrate that myelination appears necessary for mPFC-dependent cognitive processes, as lysolecithin (LPC)-induced demyelination specifically in the mPFC is sufficient to cause these behavioral and cognitive impairments. Our results indicate that chronic stress impairs cognitive functions, at least in part, through modulation of NG2(+) cell maturation and myelination, and suggest that myelination is require for normal cognitive functions.
authors.affiliation: Center for Neuropsychiatric Disorders, Institute of Life Science, Nanchang University, Nanchang 330031, PR China. Electronic address: yangyoujun123456@126.com.
authors.forename: Youjun
authors.initials: Y
authors.lastname: Yang
authors.affiliation: School of Medicine, Nanchang University, Nanchang 330031, PR China.
authors.forename: Yini
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Center for Neuropsychiatric Disorders, Institute of Life Science, Nanchang University, Nanchang 330031, PR China.
authors.forename: Fei
authors.initials: F
authors.lastname: Luo
authors.affiliation: Center for Neuropsychiatric Disorders, Institute of Life Science, Nanchang University, Nanchang 330031, PR China.
authors.forename: Baoming
authors.initials: B
authors.lastname: Li
mesh_terms: D000818:Animals; D000941:Antigens / Q000378:metabolism*; D000071183:Autophagy-Related Proteins; D001973:Bromodeoxyuridine / Q000378:metabolism; D003072:Cognition Disorders / Q000209:etiology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008569:Memory Disorders / Q000209:etiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008958:Models, Molecular; D004676:Myelin Basic Protein / Q000378:metabolism*; D016900:Neurofilament Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000378:metabolism / Q000473:pathology*; D011509:Proteoglycans / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism*; D013315:Stress, Psychological / Q000473:pathology*; D013997:Time Factors; D000099216:Chondroitin Sulfate Proteoglycan 4
chemical_list: D000941:Antigens; D000071183:Autophagy-Related Proteins; D001973:Bromodeoxyuridine; D047908:Intracellular Signaling Peptides and Proteins; D004676:Myelin Basic Protein; D016900:Neurofilament Proteins; D011509:Proteoglycans; D034741:RNA, Small Interfering; D018124:Receptors, Tumor Necrosis Factor; D000099216:Chondroitin Sulfate Proteoglycan 4; C428743:Rb1cc1 protein, mouse; C485251:Tnfrsf21 protein, mouse; C051774:neurofilament protein H
keywords: Cognitive function; Oligodendrocyte; Oligodendrocyte precursor cells; Proliferation