【摘 要】
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Objective To explore the roles of liver x receptors (LXRs) and estrogen receptors (ERs) in the activation of microglia and astrocyte in the substantia nigra (SN) of the midbrain and its relationship w
【机 构】
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Department of Physilogy, Third Military Medical University, Chongqing 400038, China
【出 处】
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中国神经科学学会第九届全国学术会议暨第五届会员代表大会
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Objective To explore the roles of liver x receptors (LXRs) and estrogen receptors (ERs) in the activation of microglia and astrocyte in the substantia nigra (SN) of the midbrain and its relationship with the degeneration of dopaminergic neurons.Methods The expression of LXRs subtypes (LXRα and LXRβ) and the ERs subtypes (ERα and ERβ) in the midbrain of mice was detected with RT-PCR and immunohistochemistry.LXRα-/-, LXRβ-/-, LXRoβ-/-mice, ovariectomy mice and wildtype mice were used in this experiment.The wildtype mice and ovariectomy mice were treated with agonist of LXR TO901317 and 17β-estradiol respectively.The protein levels of ERK and AKt were detected by Western Blot.Results (1) Both LXRα, LXRβ, ERα and ERβ are expressed in the midbrain of four-month old mice, and LXRβ is expressed at higher levels than LXRα.Immunohistochemistry confirmed the expression of LXRs and ERs.(2) Compared with age-matched WT mice, microglia and astrocyte were over-activated in LXRβ-/-and LXRαβ-/-mice, of which glia over-activation are more remarkably in the LXRα-/-β-/-mice.And the number of TH-positive neurons in the SN and TH-ir fiber density in SNpr were decreased in the LXRβ-/-, and extremely reduced in the LXRα-/-β-/-mice.(3) Intraperitoneal injection of LPS to the 4-month-old female WT mice can trigger microglia activation and release inflammatory factors such as IL-1β, IL-6 and TNF-α.LXR agonist TO901317 can effectively block the activation of microglia and reduce mRNA levels of proinflammation factors including IL-1β, IL-6 and TNF-α.(4) The number of TH-IR neurons and the gene expression level of DAT significantly decreased in ovariectomized mice, and treatment with estrogen can prevent the reduction of TH-IR.Brain derived neurotrophic factor was involved in the effect of estrogen.Conclusion By modulating the activation of microglia and astrocyte and their function of pro-inflammatory factors and neurotrophic factors level, both LXRβ and ERβ produce neurotprotection effect on dopaminergic neurons in the SN.
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