Texas A&M University, Psychiatry Department, Clinical Building 1 Suite 1100, 8441 Riverside Parkway, Bryan, TX 77807, United States; Michigan State University, United States.
Psychology Department, 293 Farm Lane, Giltner Room 108, East Lansing, MI 48824, United States; Neuroscience Program, 293 Farm Lane, Giltner Room 108, East Lansing, MI 48824, United States.
Neurosci Lett. 2021 May 14;753:135852. doi: 10.1016/j.neulet.2021.135852. Epub 2021 Mar 27.
Testosterone (T) exerts anxiolytic effects through functional androgen receptors (ARs) in rodents. T treatment of castrated mice reduces anxiety-like behavior in wild-type (WT) males, but not males with a spontaneous mutation that renders AR dysfunctional (testicular feminization mutation, Tfm). Using Cre-LoxP technology we created males carrying induced dysfunctional AR allele (induced TFM; iTfm) to determine the brain regions responsible for T-induced anxiolysis. Adult WT and iTfm mice were castrated and T treated. Castrated WTs given a blank capsule (WT + B) served as additional controls. Mice were later exposed to the anxiogenic light/dark box, sacrificed and their brains processed for immediate early gene cFos immunoreactivity. Analyses revealed that T treatment increased cFos-expressing neurons in the basolateral amygdala (blAMY) of WT males, but not in iTfm males, which did not differ from WT + B mice. In contrast, WT + T males displayed fewer cFos + cells than iTfm + T or WT + B groups in the suprachiasmatic nucleus of the hypothalamus (SCN). No effects of genotype or hormone were seen in cFos expression in the hippocampus, medial prefrontal cortex, paraventricular nucleus of the hypothalamus, oval and anterodorsal bed nucleus of the stria terminalis, or dorsal periaqueductal grey. AR immunohistochemistry indicated that ∼65 % of cells in the blAMY and SCN were AR + in WT males, so AR could act directly within neurons in these regions to modulate the animals' response to anxiogenic stimuli. Because absence of a functional AR did not affect cFos response to mild stress in the other brain regions, they are unlikely to mediate androgen's anxiolytic effects.
睾酮 (T) 通过啮齿动物中的功能性雄激素受体 (AR) 发挥抗焦虑作用。T 治疗去势雄性小鼠可减少野生型 (WT) 雄性的焦虑样行为，但不能减少 AR 功能障碍的自发性突变雄性 (睾丸女性化突变，Tfm)。我们使用 Cre-LoxP 技术创建了携带诱导性 AR 功能障碍等位基因的雄性 (诱导性 Tfm; iTfm)，以确定负责 T 诱导抗焦虑作用的脑区。成年 WT 和 iTfm 雄性被去势并接受 T 治疗。接受空白胶囊的去势 WT 雄性 (WT+B) 作为附加对照。随后，雄性被暴露于焦虑性明暗箱中，牺牲并处理其大脑以进行即时早期基因 cFos 免疫反应性检测。分析表明，T 处理增加了 WT 雄性的外侧杏仁核 (blAMY) 中表达 cFos 的神经元，但在 iTfm 雄性中则没有，后者与 WT+B 雄性没有差异。相比之下，WT+T 雄性的视交叉上核 (SCN) 中表达 cFos 的神经元少于 iTfm+T 或 WT+B 组。在海马体、内侧前额叶皮质、下丘脑室旁核、卵圆形和前背终纹床核或背侧穹窿周灰质中，基因型或激素对 cFos 表达没有影响。AR 免疫组织化学表明，WT 雄性的 blAMY 和 SCN 中约有 65%的细胞为 AR+，因此 AR 可以直接在这些区域的神经元中发挥作用，调节动物对焦虑性刺激的反应。由于 AR 功能障碍不会影响其他脑区对轻度应激的 cFos 反应，因此它们不太可能介导雄激素的抗焦虑作用。
