Neural Perturbations Associated With Recurrent Binge Alcohol in Male and Female Rats.
Neural Perturbations Associated With Recurrent Binge Alcohol in Male and Female Rats.
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雄性和雌性大鼠反复酗酒相关的神经紊乱。
DOI：
10.1111/acer.14529
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发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
Leasure JL
中科院分区：
文献类型：
--
作者：
West RK;Rodgers SP;Leasure JL
狂欢饮酒的特点是短暂的高醉和间或戒酒，这似乎对大脑特别有害。在美国女性中，酗酒的人数正在增加，但很少有临床前研究评估过酗酒对神经行为影响的性别差异。成年Long-Evans大鼠每周一次灌胃4g/kg乙醇(乙醇或等卡路里控制量)。在暴食3次或8次后收集大脑，进行成熟神经元(Neun)、小胶质细胞(Iba1)、神经发生(DCX)和反应性星形胶质细胞(Vimentin)的免疫组织化学染色。用体视学方法对海马区和内侧前额叶皮质(MPFC)的靶细胞群进行定量。在一个单独的动物队列中，在暴饮暴食3或8次后，评估了认知(空间导航和反转学习)、情感(挠痒诱发的超声波发声)和任务诱导的c-fos激活。女性(175±3.6 mg/dl)和男性(180±3.7 mg/dl)之间的血乙醇浓度没有显著差异，而且随着时间的推移也没有显著变化，表明耐受性没有形成。暴食3或8次后，两性大鼠海马齿状回颗粒神经元数量均较对照组明显减少，但对新生神经元无明显影响。此外，8次(而不是3次)暴食剂量显著增加了两性小胶质细胞总数以及海马区和mPFC中部分激活的小胶质细胞数量。在任何时间点，这两个区域都没有检测到反应性星形胶质细胞增生(波形蛋白)。酗酒对两性的行为结果都没有影响，但酗酒的大鼠在颠倒学习后显示出mPFC中细胞的激活增加。我们的数据表明，在男性和女性中，反复酗酒会导致类似的神经损伤和对酒精敏感的皮质边缘脑区的神经免疫激活。
Binge drinking, characterized by brief periods of high intoxication interspersed with periods of abstinence, appears to be particularly damaging to the brain. Binge drinking is increasing among American women, yet few preclinical studies have assessed sex differences in the neurobehavioral effects of binge alcohol. Adult Long–Evans rats were administered 4 g/kg ethanol (EtOH; or an isocaloric control dose) via intragastric gavage once-weekly. Brains were collected after 3 or 8 binge doses, and immunohistochemistry for mature neurons (NeuN), microglia (Iba1), neurogenesis (DCX), and reactive astrogliosis (vimentin) performed. Stereology was used to quantify target cell populations in the hippocampus and medial prefrontal cortex (mPFC). In a separate cohort of animals, cognition (spatial navigation and reversal learning), affect (tickling-evoked ultrasonic vocalizations), and task-induced c-fos activation were assessed after 3 or 8 binge doses. Blood EtOH concentration did not differ significantly between females (175 ± 3.6 mg/dl) and males (180 ± 3.7 mg/dl) and did not change significantly over time, indicating that tolerance did not develop. After 3 or 8 binge doses, the number of granule neurons in the hippocampal dentate gyrus of both sexes was significantly reduced in comparison with controls, although there was no binge effect on newly generated neurons. Moreover, 8 (but not 3) binge doses significantly increased the total number of microglia and the number of partially activated microglia in the hippocampus and mPFC in both sexes. There was no detectable reactive astrogliosis (vimentin) in either region at any timepoint. There was no effect of binge alcohol on behavior outcomes in either sex, but binged rats showed increased cellular activation in the mPFC following reversal learning. Our data indicate that recurrent binge alcohol results in similar neural damage and neuroimmune activation in alcohol-vulnerable corticolimbic brain regions in males and females.
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影响因子：
9.3
作者：
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通讯作者：
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影响因子：
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