Methamphetamine self-administration and voluntary exercise have opposing effects on medial prefrontal cortex gliogenesis
Methamphetamine self-administration and voluntary exercise have opposing effects on medial prefrontal cortex gliogenesis
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DOI：
10.1523/jneurosci.2505-07.2007
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发表时间：
2007-10-17
影响因子：
5.3
通讯作者：
Koob, George F.
中科院分区：
文献类型：
--
作者：
Mandyam, Chitra D.;Wee, Sunmee;Koob, George F.
滥用精神兴奋剂会导致前额皮质 (PFC) 功能缺陷，而体力活动则可以改善 PFC 依赖性认知和记忆。本研究探讨了内侧 PFC (mPFC) 前体增殖和存活对甲基苯丙胺自我给药和自愿锻炼的脆弱性，这些因素可能对 mPFC 可塑性产生相反的影响，从而促进功能后果。间歇 1 小时获取甲基苯丙胺 (I-ShA) 会增加，但每天 1 小时和 6 小时获取会减少增殖和存活，对成熟细胞表型具有剂量依赖性影响。所有组均显示细胞死亡增加。自愿运动增强了增殖和存活，但与甲基苯丙胺暴露相比，并没有改变细胞死亡或成熟表型。此外，I-ShA 和自愿运动增强的细胞存活率对少突胶质细胞与星形胶质细胞的差异调节对胶质细胞生成产生深远影响。此外，成人 mPFC 中的新细胞对神经元标记物神经元核蛋白进行染色，尽管 I-ShA 和自愿运动增强的细胞存活率并未导致神经发生增加。我们的研究结果表明，mPFC 胶质生成很容易受到精神兴奋剂滥用和体力活动的影响，其潜在机制不同。即使是中等剂量的甲基苯丙胺，mPFC 胶质生成也很敏感，这可以解释与精神兴奋剂滥用相关的明显病理学。
Psychostimulant abuse produces deficits in prefrontal cortex (PFC) function, whereas physical activity improves PFC-dependent cognition and memory. The present study explored the vulnerability of medial PFC (mPFC) precursor proliferation and survival to methamphetamine self-administration and voluntary exercise, factors that may have opposing effects on mPFC plasticity to facilitate functional consequences. Intermittent 1 h access to methamphetamine (I-ShA) increased, but daily 1 and 6 h access decreased, proliferation and survival, with dose-dependent effects on mature cell phenotypes. All groups showed increased cell death. Voluntary exercise enhanced proliferation and survival but, in contrast to methamphetamine exposure, did not alter cell death or mature phenotypes. Furthermore, enhanced cell survival by I-ShA and voluntary exercise had profound effects on gliogenesis with differential regulation of oligodendrocytes versus astrocytes. In addition, new cells in the adult mPFC stain for the neuronal marker neuronal nuclear protein, although enhanced cell survival by I-ShA and voluntary exercise did not result in increased neurogenesis. Our findings demonstrate that mPFC gliogenesis is vulnerable to psychostimulant abuse and physical activity with distinct underlying mechanisms. The susceptibility of mPFC gliogenesis to even modest doses of methamphetamine could account for the pronounced pathology linked to psychostimulant abuse.