HDAC6 dysfunction contributes to impaired maturation of adult neurogenesis in vivo: vital role on functional recovery after ischemic stroke.

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題名:	HDAC6 dysfunction contributes to impaired maturation of adult neurogenesis in vivo: vital role on functional recovery after ischemic stroke.
作者:	楊志豪 Joen-Rong Sheu, Cheng-Ying Hsieh, Thanasekaran Jayakumar, Guan-Yi Lin, Hsing-Ni Lee, Shin-Wei Huang, Chih-Hao Yang
貢獻者:	醫學系藥理學科
關鍵詞:	Keywords: Adult neurogenesis;Histone deacetylase 6;Ischemic stroke;Rehabilitation therapy;Retroviral labeling
日期:	2019-04
上傳時間:	2025-04-02 21:02:55 (UTC+8)
摘要:	Abstract Background: Promoting post-stroke neurogenesis has long been proposed to be a therapeutic strategy for the enhancement of functional recovery after cerebral ischemic stroke. Despite numerous approaches have been widely reported the proliferation or differentiation of the neurogenic population therapeutic strategies by targeting adult neurogenesis not yet to be successfully clarified in clinical settings. Here, we hypothesized that alterations in microenvironment of the ischemic brain might impede the functional maturation of adult newly generated neurons that limits functional recovery after stroke. Methods: The in vivo retroviral based labeling model was applied to directly birth-date and trace the maturation process of adult newly generating neurons after hypoxic challenge. A rehabilitation therapy procedure was adopted through the combination of task-specific motor rehabilitating training with environmental enrichment to promote functional recovery after stroke. In addition, a pharmacological or genetic suppression of HDAC6 was performed to evaluate the functional significance of HDAC6 in the pathology of ischemic stroke induced deficits. Results: Serial morphological analyses at multiple stages along the maturation process showed significant retardation of the dendritic maturation on the newly generated neurons after stroke. Subsequent biochemical analyses revealed an aberrant nuclear translocation of HDAC6 that leads to the hyper-acetylation of α-tubulin (an indication of over-stabilized microtubules) after hypoxic challenge was observed at different time points after stroke. Furthermore, the mimicry experiments with either pharmacological or genetic suppression of HDAC6, phenocopied the stroke induced retardation in dendritic maturation of newly generating neurons in vivo. More importantly, we provide direct evidence showing the proper function of HDAC6 is required for rehabilitation therapy induced therapeutic benefits after stroke. Conclusion: Together, our current study unravels that dysfunction of HDAC6 contributes to stroke induced deficits in neurogenesis and provides an innovative therapeutic strategy that targets HDAC6 for promoting functional recovery toward the patients with stroke in clinic.
關聯:	J Biomed Sci. 2019 Apr 18; 26(1): 27
描述:	【108-1 升等】臺北醫學大學教師升等專門著作職別：專任送審等級：副教授著作送審
資料類型:	article
顯示於類別:	[教師升等送審著作] 108

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