LXR agonist ameliorates depressive-like behavior through protecting hippocampal myelin repair in a mouse model of depression

【作者】 祝佩林； 唐静； 梁芯； 罗艳敏； 黎悦； 李静； 邓宇辉； 蒋林； 杨浩； 唐勇； 黄春霞；

【机构】 重庆医科大学；

【摘要】 Objective Liver X receptors(LXRs),including LXRα and LXRβ isoforms,have been demonstrated to be novel targets of antidepressants that reverse depressive behaviors.However,the potential therapeutic mechanisms by which LXR agonists ameliorate depressive behaviors are still unclear.LXRs are closely related to changes in oligodendrocytes.The current study quantitatively investigated the effects of an LXR agonist(GW3965) on hippocampal oligodendrocytes and the myelin sheath in mice with depression induced by chronic unpredictable stress(CUS).Methods Behavioral tests were executed to detect the effects of the LXR agonist,and oligodendrocytes at different stages were quantified in different hippocampal subregions using immunohistochemistry,stereological methods and immunofluorescence.Myelin basic protein(MBP) intensity was also measured by using immunofluorescence in the cornu ammonis 3(CA3) region.Results We found that depressive-like behaviors were improved after LXR activation.In addition,reductions in the numbers of newborn and mature oligodendrocytes in the hippocampal subregions and the intensity of MBP expression in the CA3 were ameliorated by treatment with the LXR agonist.Conclusions Our results suggest that improvement of oligodendrocyte differentiation and maturation and enhancement of the myelin sheath may be structural mechanisms by which the examined LXR agonist reverses depressive-like behaviors in CUS model mice.更多还原

【Abstract】 Objective Liver X receptors(LXRs),including LXRα and LXRβ isoforms,have been demonstrated to be novel targets of antidepressants that reverse depressive behaviors.However,the potential therapeutic mechanisms by which LXR agonists ameliorate depressive behaviors are still unclear.LXRs are closely related to changes in oligodendrocytes.The current study quantitatively investigated the effects of an LXR agonist(GW3965) on hippocampal oligodendrocytes and the myelin sheath in mice with depression induced by chronic unpredictable stress(CUS).Methods Behavioral tests were executed to detect the effects of the LXR agonist,and oligodendrocytes at different stages were quantified in different hippocampal subregions using immunohistochemistry,stereological methods and immunofluorescence.Myelin basic protein(MBP) intensity was also measured by using immunofluorescence in the cornu ammonis 3(CA3) region.Results We found that depressive-like behaviors were improved after LXR activation.In addition,reductions in the numbers of newborn and mature oligodendrocytes in the hippocampal subregions and the intensity of MBP expression in the CA3 were ameliorated by treatment with the LXR agonist.Conclusions Our results suggest that improvement of oligodendrocyte differentiation and maturation and enhancement of the myelin sheath may be structural mechanisms by which the examined LXR agonist reverses depressive-like behaviors in CUS model mice.更多还原