Effect of HDAC Inhibitors on Neuroprotection and Neurite Outgrowth in Primary Rat Cortical Neurons Following Ischemic Insult

被引:46
作者
Hasan, Mohammad Rakibul [1 ]
Kim, Ji-Hye [1 ]
Kim, Youn Jung [2 ]
Kwon, Kyoung Ja [1 ]
Shin, Chan Young [1 ]
Kim, Hahn Young [1 ]
Han, Seol-Heui [1 ]
Choi, Dong-Hee [1 ,3 ]
Lee, Jongmin [1 ,4 ]
机构
[1] Konkuk Univ, SMART Inst Adv Biomed Sci, Ctr Neurosci Res, Seoul 143701, South Korea
[2] Kyung Hee Univ, Coll Nursing Sci, Seoul, South Korea
[3] Konkuk Univ, Sch Med, Dept Med Sci, Seoul 143701, South Korea
[4] Konkuk Univ, Sch Med, Dept Rehabil Med, Seoul 143701, South Korea
基金
新加坡国家研究基金会;
关键词
HDAC inhibitors; Neurite outgrowth; Brain derived neurotrophic factor; Oxygen-glucose deprivation; Primary cortical neurons; HISTONE DEACETYLASE INHIBITORS; STABILIZER VALPROIC ACID; MOOD STABILIZER; SYNAPTIC PLASTICITY; CEREBRAL-ISCHEMIA; PREFRONTAL CORTEX; BCL-2; EXPRESSION; SODIUM-VALPROATE; CELL-DEATH; BRAIN;
D O I
10.1007/s11064-013-1098-9
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Histone deacetylase inhibitors (HDACi)-valproic acid (VPA) and trichostatin A (TSA) promote neurogenesis, neurite outgrowth, synaptic plasticity and neuroprotection. In this study, we investigated whether VPA and TSA promote post-ischemic neuroprotection and neuronal restoration in rat primary cortical neurons. On 6 days in vitro (DIV), cortical neurons were exposed to oxygen-glucose deprivation for 90 min. Cells were returned to normoxic conditions and cultured for 1, 3, or 7 days with or without VPA and TSA. Control cells were cultured in normoxic conditions only. On 7, 9, and 13 DIV, cells were measured neurite outgrowth using the Axiovision program and stained with Tunel staining kit. Microtubule associated protein-2 immunostaining and tunel staining showed significant recovery of neurite outgrowth and post-ischemic neuronal death by VPA or TSA treatment. We also determined levels of acetylated histone H3, PSD95, GAP 43 and synaptophysin. Significant increases in all three synaptic markers and acetylated histone H3 were observed relative to non-treated cells. Post-ischemic HDACi treatment also significantly raised levels of brain derived neurotrophic factor (BDNF) expression and secreted BDNF. Enhanced BDNF expression by HDACi treatment might have been involved in the post-ischemic neuroprotection and neuronal restorative effects. Our findings suggest that both VPA and TSA treatment during reoxygenation after ischemia may help post-ischemic neuroprotection and neuronal regeneration via increased BDNF expression and activation.
引用
收藏
页码:1921 / 1934
页数:14
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