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Molecular Neurobiology

, Volume 49, Issue 1, pp 176–186 | Cite as

Activation of Liver X Receptor Is Protective Against Ethanol-Induced Developmental Impairment of Bergmann Glia and Purkinje Neurons in the Mouse Cerebellum

  • Yang Yang
  • Yongping Tang
  • Yan Xing
  • Meina Zhao
  • Xiaohang Bao
  • Dayu Sun
  • Xiaotong Tang
  • Yuzhang Wu
  • Haiwei XuEmail author
  • Xiaotang FanEmail author
Article

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.

Keywords

Cerebellum Development Ethanol Mouse Liver X receptor 

Notes

Acknowledgments

This study was supported by the National Nature Science Foundation of China (no. 31070927 and no. 31071299) and the Foundation of the Third Military Medical University (no. 2011XQN05).

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Yang Yang
    • 1
  • Yongping Tang
    • 2
    • 3
  • Yan Xing
    • 4
  • Meina Zhao
    • 1
  • Xiaohang Bao
    • 5
  • Dayu Sun
    • 1
  • Xiaotong Tang
    • 1
  • Yuzhang Wu
    • 4
  • Haiwei Xu
    • 2
    • 3
    Email author
  • Xiaotang Fan
    • 1
    Email author
  1. 1.Department of Histology and EmbryologyThird Military Medical UniversityChongqingPeople’s Republic of China
  2. 2.Southwest Eye Hospital, Southwest HospitalThird Military Medical UniversityChongqingPeople’s Republic of China
  3. 3.Key Laboratory of Visual Damage and Regeneration and Restoration of ChongqingChongqingPeople’s Republic of China
  4. 4.Institute of Immunology, PLAThird Military Medical UniversityChongqingPeople’s Republic of China
  5. 5.Department of Anesthesiology, Xinqiao HospitalThird Military Medical UniversityChongqingPeople’s Republic of China

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