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Adolescent Ethanol Exposure Alters Cholinergic Function and Apical Dendritic Branching Within the Orbital Frontal Cortex
Neuroscience ( IF 3.3 ) Pub Date : 2021-08-24 , DOI: 10.1016/j.neuroscience.2021.08.014
B T Kipp 1 , P T Nunes 1 , E Galaj 1 , B Hitchcock 1 , T Nasra 1 , K R Poynor 1 , S K Heide 1 , N L Reitz 1 , L M Savage 1
Affiliation  

During adolescence, heavy binge-like ethanol consumption can lead to frontocortical structural and functional impairments. These impairments are likely driven by adolescence being a critical time point for maturation of brain regions associated with higher-order cognitive functioning. Rodent models of heavy binge-like ethanol exposure show consistent disruptions to the typical development of the prefrontal cortex (PFC). All deep cortical layers receive cholinergic projections that originate from the Nucleus basalis of Meynert (NbM) complex. These cholinergic projections are highly involved in learning, memory, and attention. Adolescent intermittent ethanol exposure (AIE) induces cholinergic dysfunction as a result of an epigenetic suppression of the genes that drive the cholinergic phenotype. The current study used a model of AIE to assess structural and functional changes to the frontal cortex and NbM following binge-like ethanol exposure in adolescence. Western blot analysis revealed long-term disruptions of the cholinergic circuit following AIE: choline acetyltransferase (ChAT) was suppressed in the NbM and vesicular acetylcholine transporter (VAChT) was suppressed in the orbitofrontal cortex (OFC). In vivo microdialysis for acetylcholine efflux during a spatial memory task determined changes in cholinergic modulation within the PFC following AIE. However, AIE spared performance on the spatial memory task and on an operant reversal task. In a second study, Golgi-Cox staining determined that AIE increased apical dendritic complexity in the OFC, with sex influencing whether the increase in branching occurred near or away from the soma. Spine density or maturity was not affected, likely compensating for a disruption in neurotransmitter function following AIE.



中文翻译:

青少年乙醇暴露会改变眶额皮质内的胆碱能功能和顶端树突分支

在青春期,大量的类似酗酒的乙醇消耗会导致额皮质结构和功能障碍。这些损伤可能是由青春期驱动的,青春期是与高级认知功能相关的大脑区域成熟的关键时间点。重度狂饮样乙醇暴露的啮齿动物模型显示出对前额叶皮层 (PFC) 典型发育的持续破坏。所有深层皮质层都接受源自 Meynert 基底核 (NbM) 复合体的胆碱能投射。这些胆碱能投射高度参与学习、记忆和注意力。由于驱动胆碱能表型的基因的表观遗传抑制,青少年间歇性乙醇暴露 (AIE) 会诱导胆碱能功能障碍。目前的研究使用 AIE 模型来评估在青春期酗酒后暴露于类似酒精的额叶皮层和 NbM 的结构和功能变化。蛋白质印迹分析显示 AIE 后胆碱能回路的长期中断:胆碱乙酰转移酶 (ChAT) 在 NbM 中受到抑制,而囊泡乙酰胆碱转运蛋白 (VAChT) 在眶额皮质 (OFC) 中受到抑制。空间记忆任务期间乙酰胆碱流出的体内微透析确定了 AIE 后 PFC 内胆碱能调节的变化。然而,AIE 在空间记忆任务和操作逆转任务上表现不佳。在第二项研究中,Golgi-Cox 染色确定 AIE 增加了 OFC 的顶端树突复杂性,性别影响分支的增加是发生在体细胞附近还是远离体细胞。脊柱密度或成熟度没有受到影响,可能补偿了 AIE 后神经递质功能的破坏。

更新日期:2021-09-06
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