title: Activation of liver X receptor is protective against ethanol-induced developmental impairment of Bergmann glia and Purkinje neurons in the mouse cerebellum.
abstract: Cerebellar Purkinje cell and granule cell development are coordinated by Bergmann glia, and are particularly sensitive to ethanol (EtOH) exposure. The liver X receptor (LXR) plays important roles in Bergmann glial development. However, the effect of LXR activation on EtOH-mediated impairment of Bergmann glia and subsequently on Purkinje cell dendritogenesis remains undetermined. Therefore, using immunohistochemistry, quantitative real-time PCR and Western blot, we tested the possible protection of LXR agonist T0901317 (T0) on Bergmann glia and Purkinje cell dendritogenesis in mice exposed to ethanol. Results showed that a brief exposure of EtOH on postnatal day (PD 5) significantly decreased the average body weight of mice at PD 6 without alteration in the brain weight. In EtOH-exposed mice, the number of migrating granule cells in the molecular layer was significantly decreased, and this effect was attenuated by pretreatment of T0. EtOH exposure also resulted in the significant reduction of calbindin-labeled Purkinje cells, their maximum dendrite length, and impairment of Purkinje cell dendritogenesis. Furthermore, EtOH induced the activation of microglia in the Purkinje cell layer and impaired the development of Bergmann glia. However, pretreatment of T0 effectively blocked all of these responses. These responses were found to be mediated by the inhibition of upregulated levels of β-catenin and transcription factor LEF1 in the cerebellum. Overall, the results suggest that activating LXRs on postnatal mice exposed to EtOH is protective to Bergmann glia, and thus may play a critical role in preventing EtOH-induced defects during cerebellar development.
authors.affiliation: Department of Histology and Embryology, Third Military Medical University, Chongqing, 400038, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Yongping
authors.initials: Y
authors.lastname: Tang
authors.forename: Yan
authors.initials: Y
authors.lastname: Xing
authors.forename: Meina
authors.initials: M
authors.lastname: Zhao
authors.forename: Xiaohang
authors.initials: X
authors.lastname: Bao
authors.forename: Dayu
authors.initials: D
authors.lastname: Sun
authors.forename: Xiaotong
authors.initials: X
authors.lastname: Tang
authors.forename: Yuzhang
authors.initials: Y
authors.lastname: Wu
authors.forename: Haiwei
authors.initials: H
authors.lastname: Xu
authors.forename: Xiaotang
authors.initials: X
authors.lastname: Fan
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002531:Cerebellum / Q000254:growth & development / Q000378:metabolism* / Q000473:pathology; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D006845:Hydrocarbons, Fluorinated / Q000494:pharmacology; D000071518:Liver X Receptors; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D057093:Orphan Nuclear Receptors / Q000819:agonists / Q000378:metabolism*; D011689:Purkinje Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D011897:Random Allocation; D013449:Sulfonamides / Q000494:pharmacology; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
chemical_list: D000431:Ethanol; D006845:Hydrocarbons, Fluorinated; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D013449:Sulfonamides; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
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