Aoki C, Wable G, Chowdhury T G, Sabaliauskas N A, Laurino K, Barbarich-Marsteller N C
Center for Neural Science, New York University, New York, NY 10003, United States.
Center for Neural Science, New York University, New York, NY 10003, United States.
Neuroscience. 2014 Apr 18;265:108-23. doi: 10.1016/j.neuroscience.2014.01.011. Epub 2014 Jan 18.
Anorexia nervosa (AN) is a psychiatric illness characterized by restricted eating and an intense fear of gaining weight. Most individuals with AN are females, diagnosed first during adolescence, 40-80% of whom exhibit excessive exercise, and an equally high number with a history of anxiety disorder. We sought to determine the cellular basis for individual differences in AN vulnerability by using an animal model, activity-based anorexia (ABA), that is induced by combining food restriction (FR) with access to a running wheel that allows voluntary exercise. Previously, we showed that by the fourth day of FR, the ABA group of adolescent female rats exhibit >500% greater levels of non-synaptic α4βδ-GABAARs at the plasma membrane of hippocampal CA1 pyramidal cell spines, relative to the levels found in age-matched controls that are not FR and without wheel access. Here, we show that the ABA group exhibits individual differences in body weight loss, with some losing nearly 30%, while others lose only 15%. The individual differences in weight loss are ascribable to individual differences in wheel activity that both precedes and concurs with days of FR. Moreover, the increase in activity during FR correlates strongly and negatively with α4βδ-GABAAR levels (R=-0.9, p<0.01). This negative correlation is evident within 2days of FR, before body weight loss approaches life-threatening levels for any individual. These findings suggest that increased shunting inhibition by α4βδ-GABAARs in spines of CA1 pyramidal neurons may participate in the protection against the ABA-inducing environmental factors of severe weight loss by suppressing excitability of the CA1 pyramidal neurons which, in turn, is related indirectly to suppression of excessive exercise. The data also indicate that, although exercise has many health benefits, it can be maladaptive to individuals with low levels of α4βδ-GABAARs in the CA1, particularly when combined with FR.
神经性厌食症（AN）是一种精神疾病，其特征为饮食受限以及对体重增加的强烈恐惧。大多数患有AN的个体为女性，首次诊断多在青春期，其中40 - 80%的人有过度运动的表现，且有焦虑症病史的人数也同样众多。我们试图通过使用一种动物模型——基于活动的厌食症（ABA）来确定AN易感性个体差异的细胞基础，该模型是通过将食物限制（FR）与可自愿运动的跑步轮相结合诱导产生的。此前，我们发现，到FR的第四天，与未进行FR且没有跑步轮的年龄匹配对照组相比，ABA组的青春期雌性大鼠海马CA1锥体细胞棘突质膜上的非突触α4βδ - GABA受体水平高出500%以上。在此，我们表明ABA组在体重减轻方面存在个体差异，一些个体体重减轻近30%，而另一些个体仅减轻15%。体重减轻的个体差异可归因于FR之前和期间跑步轮活动的个体差异。此外，FR期间活动的增加与α4βδ - GABA受体水平呈强烈负相关（R = -0.9，p < 0.01）。这种负相关在FR的2天内就很明显，此时任何个体的体重减轻尚未达到危及生命的水平。这些发现表明，CA1锥体细胞棘突中α4βδ - GABA受体增加的分流抑制可能通过抑制CA1锥体细胞的兴奋性参与预防由ABA诱导的严重体重减轻的环境因素，而这又间接与过度运动的抑制有关。数据还表明，尽管运动有许多健康益处，但对于CA1中α4βδ - GABA受体水平较低的个体可能是适应不良的，特别是与FR相结合时。
