Department of Psychiatry, College of Physicians and Surgeons of Columbia University, 1051 Riverside Drive, Unit 98, New York, NY 10032, United States; New York State Psychiatric Institute, 1051 Riverside Drive, Unit 98, New York, NY 10032, United States.
Princeton Neuroscience Institute, Princeton University, Princeton, NJ 08544, United States.
Behav Brain Res. 2013 Jan 1;236(1):251-257. doi: 10.1016/j.bbr.2012.08.047. Epub 2012 Sep 4.
Activity-based anorexia (ABA) is an animal model of anorexia nervosa that mimics core features of the clinical psychiatric disorder, including severe food restriction, weight loss, and hyperactivity. The ABA model is currently being used to study starvation-induced changes in the brain. Here, we examined hippocampal cell proliferation in animals with ABA (or the appropriate control conditions). Adolescent female Sprague-Dawley rats were assigned to 4 groups: control (24h/day food access), food-restricted (1h/day food access), exercise (24h/day food and wheel access), and ABA (1h/day food access, 24h/day wheel access). After 3 days of ABA, 5-bromo-2'-deoxyuridine (BrdU; 200mg/kg, i.p.) was injected and the rats were perfused 2h later. Brains were removed and subsequently processed for BrdU and Ki67 immunohistochemistry. The acute induction of ABA reduced cell proliferation in the dentate gyrus. This effect was significant in the hilus region of the dentate gyrus, but not in the subgranular zone, where adult neurogenesis occurs. Marked decreases in cell proliferation were also observed in the surrounding dorsal hippocampus and in the corpus callosum. These results indicate a primary effect on gliogenesis rather than neurogenesis following 3 days of ABA. For each brain region studied (except SGZ), there was a strong positive correlation between the level of cell proliferation and body weight/food intake. Future studies should examine whether these changes are maintained following long-term weight restoration and whether alterations in neurogenesis occur following longer exposures to ABA.
活动限制型厌食症（ABA）是一种模仿神经性厌食症核心特征的动物模型，包括严重的食物限制、体重减轻和过度活跃。ABA 模型目前正被用于研究饥饿对大脑的影响。在这里，我们研究了 ABA 动物模型中海马细胞增殖的变化（或适当的对照条件）。将青春期雌性 Sprague-Dawley 大鼠分为 4 组：对照组（每天 24 小时进食）、限食组（每天 1 小时进食）、运动组（每天 24 小时进食和轮式活动）和 ABA 组（每天 1 小时进食，24 小时轮式活动）。在 ABA 进行 3 天后，大鼠腹腔注射 5-溴-2'-脱氧尿苷（BrdU；200mg/kg），2 小时后进行灌注。取出大脑，随后进行 BrdU 和 Ki67 免疫组织化学处理。急性诱导的 ABA 减少了齿状回的细胞增殖。这种影响在齿状回的门区明显，但在发生成年神经发生的颗粒下区不明显。细胞增殖也明显减少，发生在周围的海马背侧和胼胝体。这些结果表明，在 ABA 进行 3 天后，主要影响神经胶质发生，而不是神经发生。对于研究的每个脑区（除 SGZ 外），细胞增殖水平与体重/食物摄入量之间存在强烈的正相关。未来的研究应该检查这些变化是否在长期体重恢复后仍然存在，以及在更长时间暴露于 ABA 后是否会发生神经发生的改变。
