Temporally specific burst in cell proliferation increases hippocampal neurogenesis in protracted abstinence from alcohol
Temporally specific burst in cell proliferation increases hippocampal neurogenesis in protracted abstinence from alcohol
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DOI：
10.1523/jneurosci.3063-04.2004
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发表时间：
2004-10-27
影响因子：
5.3
通讯作者：
Crews, FT
中科院分区：
文献类型：
--
作者：
Nixon, K;Crews, FT
成人神经发生是一种新的可塑性形式，可能有助于精神疾病的脑功能障碍。慢性酒精中毒是一种影响8%以上成年人的疾病，会导致认知障碍和脑容量减少，这两种情况在戒酒期间都会部分逆转。临床数据和动物模型表明海马体是学习和记忆的重要区域。在酒精依赖模型（慢性暴饮暴食暴露4天），我们表明，成人神经发生抑制依赖与新的海马神经元形成显着增加后，戒酒周。这种增加可归因于禁欲第7天细胞增殖的时间和区域特异性四倍增加，其中大多数细胞存活并以与对照相似的百分比分化，这使得新神经元的形成增加了一倍。虽然细胞增殖的增加与酒精戒断严重程度相关，但当使用地西泮（10 mg/kg）降低戒断严重程度时，细胞增殖仍然增加。事实上，那些几乎没有戒断活动的动物在戒断的第7天仍然显示出细胞增殖的两倍爆发。因此，酒精依赖和恢复依赖继续改变戒断期间海马可塑性。因为神经发生可能有助于海马功能和/或学习、记忆和情绪，所以代偿性神经发生和正常神经发生的恢复也可能对海马结构和功能产生影响。这些数据第一次提供了一种神经生物学机制，可能是人类认知功能和与成瘾恢复相关的脑容量恢复的基础。
Adult neurogenesis is a newly considered form of plasticity that could contribute to brain dysfunction in psychiatric disease. Chronic alcoholism, a disease affecting over 8% of the adult population, produces cognitive impairments and decreased brain volumes, both of which are partially reversed during abstinence. Clinical data and animal models implicate the hippocampus, a region important in learning and memory. In a model of alcohol dependence ( chronic binge exposure for 4 d), we show that adult neurogenesis is inhibited during dependence with a pronounced increase in new hippocampal neuron formation after weeks of abstinence. This increase is attributable to a temporally and regionally specific fourfold increase in cell proliferation at day 7 of abstinence, with a majority of those cells surviving and differentiating at percentages similar to controls, effects that doubled the formation of new neurons. Although increases in cell proliferation correlated with alcohol withdrawal severity, proliferation remained increased when diazepam (10 mg/kg) was used to reduce withdrawal severity. Indeed, those animals with little withdrawal activity still show a twofold burst in cell proliferation at day 7 of abstinence. Thus, alcohol dependence and recovery from dependence continues to alter hippocampal plasticity during abstinence. Because neurogenesis may contribute to hippocampal function and/or learning, memory, and mood, compensatory neurogenesis and the return of normal neurogenesis may also have an impact on hippocampal structure and function. For the first time, these data provide a neurobiological mechanism that may underlie the return of human cognitive function and brain volume associated with recovery from addiction.