Cholinergic and Neuroimmune Signaling Interact to Impact Adult Hippocampal Neurogenesis and Alcohol Pathology Across Development.
Cholinergic and Neuroimmune Signaling Interact to Impact Adult Hippocampal Neurogenesis and Alcohol Pathology Across Development.
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DOI：
10.3389/fphar.2022.849997
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发表时间：
2022
影响因子：
5.6
通讯作者：
Crews FT
中科院分区：
文献类型：
--
作者：
Macht VA;Vetreno RP;Crews FT
酒精（乙醇）的使用和滥用是一个代价高昂的社会问题，可能影响一个人的一生。酒精的使用和滥用通常始于青春期，并通常持续到成年期。酒精不仅是青少年滥用最广泛的药物，而且也是世界上滥用最广泛的药物之一。事实上，在西方世界，孕产妇饮酒率高使得发育期乙醇暴露成为神经功能缺陷最可预防的原因。临床前研究已确定，乙醇最一致的作用之一是破坏海马神经发生。然而，乙醇对海马神经发生影响的严重性、持久性和可逆性取决于暴露的发育阶段和评估时的年龄。使乙醇对神经发育的影响变得复杂的是调节神经发生的神经调节系统，特别是胆碱能系统的同时发育和成熟。海马中的胆碱能信号通过毒蕈碱和烟碱受体作用直接调节海马神经发生，并通过对海马环境环境提供抗炎调节控制来间接调节神经发生。因此，本综述旨在评估胆碱能系统成熟模式的转变及其对神经免疫信号传导的调节如何影响乙醇对成人神经发生的影响。例如，围产期乙醇暴露会减少基底前脑胆碱能神经元数量，导致海马体的长期发育障碍，并持续到成年期。在环境、发育和药理学挑战之后，成年海马神经发生的过度神经免疫反应和破坏是显而易见的，这表明围产期乙醇暴露会诱发成年期的神经源性缺陷，这种缺陷在神经和免疫功能紧张的条件下可能会被暴露出来。同样，青少年接触乙醇会持续减少基底前脑胆碱能神经元数量，增加海马神经免疫基因表达，并减少成年期海马神经发生。围产期和青少年乙醇的影响都不会因戒酒而减轻，而成人乙醇暴露引起的海马神经发生减少在戒酒后会恢复，这表明乙醇引起的神经发生和可逆性改变取决于发育时期。因此，本综述的重点是检查关键发育时期的乙醇暴露如何扰乱胆碱能和神经炎症系统的成熟，从而对成年期的海马神经发生产生不同的影响。
Alcohol (ethanol) use and misuse is a costly societal issue that can affect an individual across the lifespan. Alcohol use and misuse typically initiates during adolescence and generally continues into adulthood. Not only is alcohol the most widely abused drug by adolescents, but it is also one of the most widely abused drugs in the world. In fact, high rates of maternal drinking make developmental ethanol exposure the most preventable cause of neurological deficits in the Western world. Preclinical studies have determined that one of the most consistent effects of ethanol is its disruption of hippocampal neurogenesis. However, the severity, persistence, and reversibility of ethanol’s effects on hippocampal neurogenesis are dependent on developmental stage of exposure and age at assessment. Complicating the neurodevelopmental effects of ethanol is the concurrent development and maturation of neuromodulatory systems which regulate neurogenesis, particularly the cholinergic system. Cholinergic signaling in the hippocampus directly regulates hippocampal neurogenesis through muscarinic and nicotinic receptor actions and indirectly regulates neurogenesis by providing anti-inflammatory regulatory control over the hippocampal environmental milieu. Therefore, this review aims to evaluate how shifting maturational patterns of the cholinergic system and its regulation of neuroimmune signaling impact ethanol’s effects on adult neurogenesis. For example, perinatal ethanol exposure decreases basal forebrain cholinergic neuron populations, resulting in long-term developmental disruptions to the hippocampus that persist into adulthood. Exaggerated neuroimmune responses and disruptions in adult hippocampal neurogenesis are evident after environmental, developmental, and pharmacological challenges, suggesting that perinatal ethanol exposure induces neurogenic deficits in adulthood that can be unmasked under conditions that strain neural and immune function. Similarly, adolescent ethanol exposure persistently decreases basal forebrain cholinergic neuron populations, increases hippocampal neuroimmune gene expression, and decreases hippocampal neurogenesis in adulthood. The effects of neither perinatal nor adolescent ethanol are mitigated by abstinence whereas adult ethanol exposure-induced reductions in hippocampal neurogenesis are restored following abstinence, suggesting that ethanol-induced alterations in neurogenesis and reversibility are dependent upon the developmental period. Thus, the focus of this review is an examination of how ethanol exposure across critical developmental periods disrupts maturation of cholinergic and neuroinflammatory systems to differentially affect hippocampal neurogenesis in adulthood.
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影响因子：
2.9
作者：
BENBARAK, J;DUDAI, Y
通讯作者：
DUDAI, Y
影响因子：
3.3
作者：
Anderson ML;Nokia MS;Govindaraju KP;Shors TJ
通讯作者：
Shors TJ
影响因子：
--
作者：
Agartz, I;Momenan, R;Hommer, DW
通讯作者：
Hommer, DW
DOI：
10.1111/acer.12082
发表时间：
2013-07
期刊：
Alcoholism, clinical and experimental research
影响因子：
--
作者：
Bekdash RA;Zhang C;Sarkar DK
通讯作者：
Sarkar DK
DOI：
10.1111/acer.13545
发表时间：
2018-01
期刊：
Alcoholism, clinical and experimental research
影响因子：
--
作者：
Beattie MC;Reguyal CS;Porcu P;Daunais JB;Grant KA;Morrow AL
通讯作者：
Morrow AL