| First Author | Chen YW | Year | 2018 |
| Journal | Mol Cell Neurosci | Volume | 90 |
| Pages | 33-48 | PubMed ID | 29684457 |
| Mgi Jnum | J:268621 | Mgi Id | MGI:6269979 |
| Doi | 10.1016/j.mcn.2018.04.008 | Citation | Chen YW, et al. (2018) alpha4-GABAA receptors of hippocampal pyramidal neurons are associated with resilience against activity-based anorexia for adolescent female mice but not for males. Mol Cell Neurosci 90:33-48 |
| abstractText | Activity-based anorexia (ABA) is an animal model of anorexia nervosa, a mental illness with highest mortality and with onset that is most frequently during adolescence. We questioned whether vulnerability of adolescent mice to ABA differs between sexes and whether individual differences in resilience are causally linked to alpha4betadelta-GABAAR expression. C57BL6/J WT and alpha4-KO adolescent male and female mice underwent ABA induction by combining wheel access with food restriction. ABA vulnerability was measured as the extent of food restriction-evoked hyperactivity on a running wheel and body weight losses. alpha4betadelta-GABAAR levels at plasma membranes of pyramidal cells in dorsal hippocampus were assessed by electron microscopic immunocytochemistry. Temporal patterns and extent of weight loss during ABA induction were similar between sexes. Both sexes also exhibited individual differences in ABA vulnerability. Correlation analyses revealed that, for both sexes, body weight changes precede and thus are likely to drive suppression of wheel running. However, the suppression was during the food-anticipatory hours for males, while for females, suppression was delayed by a day and during food-access hours. Correspondingly, only females adaptively increased food intake. ABA induced up-regulation of alpha4betadelta-GABAARs at plasma membranes of dorsal hippocampal pyramidal cells of females, and especially those females exhibiting resilience. Conversely, alpha4-KO females exhibited greater food restriction-evoked hyperactivity than WT females. In contrast, ABA males did not up-regulate alpha4betadelta-GABAARs, did not exhibit genotype differences in vulnerability, and exhibited no correlation between plasmalemmal alpha4betadelta-GABAARs and ABA resilience. Thus, food restriction-evoked hyperactivity is driven by anxiety but can be suppressed through upregulation of hippocampal alpha4betadelta-GABAARs for females but not for males. This knowledge of sex-related differences in the underlying mechanisms of resilience to ABA indicates that drugs targeting alpha4betadelta-GABAARs may be helpful for treating stress-induced anxiety and anorexia nervosa of females but not males. |
