13-Cis-retinoic acid decreases hypothalamic cell number in vitro

13-Cis-retinoic acid (13-cis-RA) causes depression-related behavior in mice. Hypothalamic dysregulation has been implicated in clinical depression. In fact, apoptosis of hypothalamic neurons may lead to depression after myocardial infarction. Our objective was to determine if 13-cis-RA affects cultured hypothalamic cell number. Treatment of GT1-7 hypothalamic cells with 10 μM 13-cis-RA for 48 h decreased cell growth to 45.6 ± 13% of control. To determine if this decrease in cell number was due to 13-cis-RA acting as an oxidant, cells were treated with 13-cis-RA and ascorbic acid or butylated hydroxyanisole (BHA) for 24 or 48 h. Neither antioxidant alleviated the inhibitory affects of 13-cis-RA. In addition, 13-cis-RA treatment did not increase superoxide anion production, indicating 13-cis-RA was not acting as an oxidant. To determine if 13-cis-RA was acting via retinoic acid receptors (RARs) to decrease cell number, GT1-7 cells were treated with 13-cis-RA and the RAR pan-antagonist, AGN 193109. Treatment with the RAR-antagonist blocked the ability of 13-cis-RA to decrease cell number, indicating this phenomenon was a RAR-independent mechanism. We hypothesize that the ability of 13-cis-RA to decrease hypothalamic cell number may contribute to the increased depression-related behaviors observed in mice.