title: LXR agonist rescued the deficit in the proliferation of the cerebellar granule cells induced by dexamethasone.
abstract: Dexamethasone (DEX) exposure during early postnatal life produces permanent neuromotor and intellectual deficits and stunts cerebellar growth. The liver X receptor (LXR) plays important roles in CNS development. However, the effects of LXR on the DEX-mediated impairment of cerebellar development remain undetermined. Thus, mice were pretreated with LXR agonist TO901317 (TO) and were later exposed to DEX to evaluate its protective effects on DEX-mediated deficit during cerebellar development. The results showed that an acute exposure of DEX on postnatal day 7 resulted in a significant impairment in cerebellar development and decreased the proliferation of granule neuron precursors in the external granule layer of cerebellum. This effect was attenuated by pretreatment with TO. We further found that the decrease in the proliferation caused by DEX occurred via up-regulation of glucocorticoid receptor and p27kip1, which could be partially prevented by LXR agonist pretreatment. Overall, our results suggest that LXR agonist pretreatment could protect against DEX-induced deficits in cerebellar development in postnatal mice and may thus be perspective recruited to counteract such GC side effects.
authors.affiliation: Department of Developmental Neuropsychology, School of Psychology, Third Military Medical University, Chongqing, 400038, China.
authors.forename: Xuting
authors.initials: X
authors.lastname: Bian
authors.affiliation: Department of Developmental Neuropsychology, School of Psychology, Third Military Medical University, Chongqing, 400038, China.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Zhong
authors.affiliation: Department of Developmental Neuropsychology, School of Psychology, Third Military Medical University, Chongqing, 400038, China.
authors.forename: Fen
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Developmental Neuropsychology, School of Psychology, Third Military Medical University, Chongqing, 400038, China.
authors.forename: Yulong
authors.initials: Y
authors.lastname: Cai
authors.affiliation: Department of Developmental Neuropsychology, School of Psychology, Third Military Medical University, Chongqing, 400038, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Developmental Neuropsychology, School of Psychology, Third Military Medical University, Chongqing, 400038, China.
authors.forename: Lian
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Developmental Neuropsychology, School of Psychology, Third Military Medical University, Chongqing, 400038, China. Electronic address: fanxiaotang2005@163.com.
authors.forename: Xiaotang
authors.initials: X
authors.lastname: Fan
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D002531:Cerebellum / Q000187:drug effects / Q000473:pathology*; D003907:Dexamethasone / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006845:Hydrocarbons, Fluorinated / Q000008:administration & dosage*; D000071518:Liver X Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000008:administration & dosage; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013449:Sulfonamides / Q000008:administration & dosage*; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
chemical_list: D003907:Dexamethasone; D006845:Hydrocarbons, Fluorinated; D000071518:Liver X Receptors; D018696:Neuroprotective Agents; D013449:Sulfonamides; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
keywords: Cerebellum; Development; Dexamethasone; LXR; Proliferation