Alcohol inhibition of neurogenesis: a mechanism of hippocampal neurodegeneration in an adolescent alcohol abuse model.
Alcohol inhibition of neurogenesis: a mechanism of hippocampal neurodegeneration in an adolescent alcohol abuse model.
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DOI：
10.1002/hipo.20665
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发表时间：
2010-05
期刊：
影响因子：
3.5
通讯作者：
Nixon, Kimberly
中科院分区：
文献类型：
--
作者：
Morris, Stephanie A.;Eaves, David W.;Smith, Aleksander R.;Nixon, Kimberly
被诊断患有酒精使用障碍的青少年的海马体出现神经退行性变，海马体是学习、记忆和情绪调节的重要区域。这项研究探讨了过量饮酒（酒精使用障碍的特征）导致神经退行性病变的潜在机制。由于海马神经干细胞是持续神经发生的基础，这种现象有助于海马结构和功能，因此我们研究了酒精使用障碍的青少年大鼠模型中细胞死亡和细胞诞生的各个方面。使用各种标记物的免疫组织化学以及溴脱氧尿苷（BrdU）注射来检查神经发生的不同方面。根据双皮质素表达，暴饮酒精暴露 4 天后，最后一次给药后第 0 天和第 2 天，神经发生减少了 33% 和 28%。为了确定神经发生的减少是否是由于神经干细胞增殖的影响，对 BrdU 标记的细胞进行定量显示，暴露于酒精的大脑中齿状回减少了 21%。酒精暴露后 28 天评估了 BrdU 标记细胞的细胞存活率和表型，结果显示酒精暴露组的存活细胞数量显着减少了 50%。固缩、FluoroJade B 阳性和 TUNEL 阳性细胞数量的显着增加支持了存活率的降低。然而，TUNEL 阳性细胞很少，因此在该模型中细胞死亡很可能是坏死。尽管酒精减少了新生细胞的数量，但它并不影响成熟为神经元（分化）的细胞的百分比。因此，我们的数据支持，在青少年酒精使用障碍模型中，神经发生受到两种机制的损害：酒精对神经干细胞增殖的抑制和酒精对新细胞存活的影响。值得注意的是，酒精对神经发生的抑制可能超过每个切片中少数濒临死亡的细胞，这意味着酒精对神经发生的抑制会导致酒精使用障碍中的海马神经变性。
Adolescents diagnosed with an alcohol use disorder show neurodegeneration in the hippocampus, a region important for learning, memory, and mood regulation. This study examines a potential mechanism by which excessive alcohol intake, characteristic of an alcohol use disorder, produces neurodegeneration. As hippocampal neural stem cells underlie ongoing neurogenesis, a phenomenon that contributes to hippocampal structure and function, we investigated aspects of cell death and cell birth in an adolescent rat model of an alcohol use disorder. Immunohistochemistry of various markers along with Bromo-deoxy-Uridine (BrdU) injections were used to examine different aspects of neurogenesis. After 4 days of binge alcohol exposure, neurogenesis was decreased by 33% and 28% at 0 and 2 days after the last dose according to doublecortin expression. To determine whether this decrease in neurogenesis was due to effects on neural stem cell proliferation, quantification of BrdU-labeled cells revealed a 21% decrease in the dentate gyrus of alcohol-exposed brains. Cell survival and phenotype of BrdU-labeled cells were assessed 28 days after alcohol exposure and revealed a significant, 50% decrease in the number of surviving cells in the alcohol-exposed group. Reduced survival was supported by significant increases in the number of pyknotic-, FluoroJade B positive-, and TUNEL-positive cells. However, so few cells were TUNEL-positive that cell death is likely necrotic in this model. Although alcohol decreased the number of newborn cells, it did not affect the percentage of cells that matured into neurons (differentiation). Thus, our data support that in a model of an adolescent alcohol use disorder, neurogenesis is impaired by two mechanisms: alcohol-inhibition of neural stem cell proliferation and alcohol effects on new cell survival. Remarkably, alcohol inhibition of neurogenesis may outweigh the few dying cells per section, which implies that alcohol inhibition of neurogenesis contributes to hippocampal neurodegeneration in alcohol use disorders.
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DOI：
10.1073/pnas.120552597
发表时间：
2000-06-20
影响因子：
11.1
作者：
Eisch, AJ;Barrot, M;Nestler, EJ
通讯作者：
Nestler, EJ
影响因子：
2.5
作者：
Dayer, AG;Ford, AA;Cameron, HA
通讯作者：
Cameron, HA
影响因子：
2.5
作者：
Brown, JP;Couillard-Després, S;Kuhn, HG
通讯作者：
Kuhn, HG
DOI：
10.1083/jcb.119.3.493
发表时间：
1992-11
期刊：
The Journal of cell biology
影响因子：
--
作者：
Gavrieli Y;Sherman Y;Ben-Sasson SA
通讯作者：
Ben-Sasson SA
DOI：
10.1097/01.alc.0000164381.67723.76
发表时间：
2005-05-01
期刊：
ALCOHOL-CLINICAL AND EXPERIMENTAL RESEARCH
影响因子：
--
作者：
Harford, TC;Grant, BF;Chen, CM
通讯作者：
Chen, CM