Reitz Nicole L, Nunes Polliana T, Savage Lisa M
Department of Psychology, Binghamton University - State University of New York, Binghamton, NY, United States.
Front Behav Neurosci. 2021 Oct 22;15:772857. doi: 10.3389/fnbeh.2021.772857. eCollection 2021.
Heavy alcohol consumption followed by periods of abstinence (i.e., binge drinking) during adolescence is a concern for both acute and chronic health issues. Persistent brain damage after adolescent intermittent ethanol exposure in rodents, a model of binge drinking, includes reduced hippocampal neurogenesis and a loss of neurons in the basal forebrain that express the cholinergic phenotype. The circuit formed between those regions, the septohippocampal pathway, is critical for learning and memory. Furthermore, this circuit is also altered during the aging process. Thus, we examined whether pathology in septohippocampal circuit and impairments in spatial behaviors are amplified during aging following adolescent intermittent ethanol exposure. Female and male rats were exposed to intermittent intragastric gavage of water (control) or 20% ethanol (dose of 5 g/kg) for a 2 days on/off cycle from postnatal days 25-55. Either 2 (young adult) or 12-14 (middle-age) months post exposure, rats were tested on two spatial tasks: spontaneous alternation and novel object in place. Acetylcholine efflux was assessed in the hippocampus during both tasks. There was no adolescent ethanol-induced deficit on spontaneous alternation, but middle-aged male rats displayed lower alternation rates. Male rats exposed to ethanol during adolescence had blunted behavioral evoked acetylcholine during spontaneous alternation testing. All ethanol-exposed rats displayed suppression of the cholinergic neuronal phenotype. On the novel object in place task, regardless of sex, ethanol-exposed rats performed significantly worse than control-treated rats, and middle aged-rats, regardless of sex or ethanol exposure, were significantly impaired relative to young adult rats. These results indicate that male rats display earlier age-related cognitive impairment on a working memory task. Furthermore, male rats exposed to ethanol during adolescence have blunted behavior-evoked hippocampal acetylcholine efflux. In addition, middle-aged and ethanol-exposed rats, regardless of sex, are impaired at determining discrete spatial relationship between objects. This type of pattern separation impairment was associated with a loss of neurogenesis. Thus, binge-type adolescent ethanol exposure does affect the septohippocampal circuit, and can accelerate age-related cognitive impairment on select spatial tasks.
青春期大量饮酒后又经历戒酒期（即暴饮），这对急性和慢性健康问题而言都是一个值得关注的情况。在啮齿动物中，青春期间歇性乙醇暴露（一种暴饮模型）后会出现持续性脑损伤，包括海马神经发生减少以及基底前脑表达胆碱能表型的神经元丧失。这些区域之间形成的回路，即隔海马通路，对学习和记忆至关重要。此外，该回路在衰老过程中也会发生改变。因此，我们研究了青春期间歇性乙醇暴露后，衰老过程中隔海马回路的病理变化和空间行为障碍是否会加剧。从出生后第25天至55天，对雌性和雄性大鼠进行间歇性灌胃，分别给予水（对照）或20%乙醇（剂量为5 g/kg），以2天给药/2天停药的周期进行。在暴露后2个月（年轻成年期）或12 - 14个月（中年期），对大鼠进行两项空间任务测试：自发交替和新物体定位。在两项任务过程中，均评估海马中的乙酰胆碱流出情况。青春期乙醇暴露并未导致自发交替出现缺陷，但中年雄性大鼠的交替率较低。青春期暴露于乙醇的雄性大鼠在自发交替测试中，行为诱发的乙酰胆碱反应减弱。所有暴露于乙醇的大鼠均表现出胆碱能神经元表型受到抑制。在新物体定位任务中，无论性别如何，暴露于乙醇的大鼠表现均明显比对照处理的大鼠差，并且中年大鼠，无论性别或是否暴露于乙醇，相对于年轻成年大鼠均明显受损。这些结果表明，雄性大鼠在工作记忆任务中表现出与年龄相关的更早认知障碍。此外，青春期暴露于乙醇的雄性大鼠行为诱发的海马乙酰胆碱流出减弱。此外，无论性别，中年和暴露于乙醇的大鼠在确定物体之间离散空间关系方面均存在障碍。这种模式分离障碍与神经发生减少有关。因此，青春期暴饮型乙醇暴露确实会影响隔海马回路，并可加速与年龄相关的特定空间任务的认知障碍。
