Division of Reproductive Sciences, Oregon National Primate Research Center, Beaverton, OR 97006, United States.
Prog Neuropsychopharmacol Biol Psychiatry. 2013 Jul 1;44:143-53. doi: 10.1016/j.pnpbp.2013.01.013. Epub 2013 Jan 26.
Female cynomolgus monkeys exhibit different degrees of reproductive dysfunction with moderate metabolic and psychosocial stress. When stressed with a paradigm of relocation and diet for 60 days, or 2 menstrual cycles, highly stress resilient monkeys continue to ovulate during both stress cycles (HSR); medium stress resilient monkeys ovulate once (MSR) and stress sensitive monkeys do not ovulate for the entire 60 days (SS). This study examines serotonin-related gene expression in monkeys with different sensitivity to stress and exposed to 5 days of moderate stress. Monkeys were first characterized as HSR, MSR or SS. After resumption of menstrual cycles, each monkey was re-stressed for 5 days in the early follicular phase. The expression of 3 genes pivotal to serotonin neural function was assessed in the 3 groups of monkeys (n=4-5/group). Tryptophan hydroxylase 2 (TPH2), the serotonin reuptake transporter (SERT), and the 5HT1A autoreceptor mRNAs expression were determined at 4 morphological levels of the dorsal raphe nucleus with in situ hybridization (ISH) using digoxigenin-incorporated riboprobes. In addition, cFos was examined with immunohistochemistry. Positive pixel area and/or cell number were measured. All data were analyzed with ANOVA (3 groups) and with a t-test (2 groups). After 5 days of stress, TPH2, SERT, 5HT1A and cFos were significantly lower in the SS group than the HSR group (p<0.05, all). This pattern of expression was the same as the pattern observed in the absence of stress in previous studies. Therefore, the ratio of the HSR/SS expression of each serotonergic gene was calculated in the presence and absence of stress. There was little or no difference in the ratio of HSR/SS gene expression in the presence or absence of stress. Moreover, cFos expression indicates that overall, cell activation in the dorsal raphe nucleus and periaquaductal gray is lower in SS than HSR animals. These data suggest that the serotonin system may set the sensitivity or resilience of the individual, but serotonin-related gene expression may not rapidly respond to moderate stress in nonhuman primates.
雌性食蟹猴在受到中度代谢和心理社会压力时会表现出不同程度的生殖功能障碍。当受到 60 天的搬迁和饮食范式或 2 个月经周期的压力时，高压力适应猴在两个压力周期中继续排卵（HSR）；中压力适应猴排卵一次（MSR），而压力敏感猴在整个 60 天内不排卵（SS）。本研究检查了对压力具有不同敏感性并暴露于 5 天中度压力的猴子中与 5-羟色胺相关的基因表达。首先将猴子分为 HSR、MSR 或 SS。在月经周期恢复后，每只猴子在卵泡早期再次经历 5 天的应激。在 3 组猴子（n=4-5/组）中评估了对 5-羟色胺神经功能至关重要的 3 个基因的表达。色氨酸羟化酶 2（TPH2）、5-羟色胺再摄取转运体（SERT）和 5-HT1A 自身受体 mRNA 的表达用原位杂交（ISH）用 DIG 标记的探针在背侧中缝核的 4 个形态学水平上进行测定。此外，用免疫组织化学检查 cFos。测量阳性像素面积和/或细胞数。所有数据均采用 ANOVA（3 组）和 t 检验（2 组）进行分析。应激 5 天后，SS 组 TPH2、SERT、5HT1A 和 cFos 的表达明显低于 HSR 组（p<0.05，全部）。这种表达模式与先前研究中无应激时观察到的模式相同。因此，在存在和不存在应激的情况下计算了每个 5-羟色胺能基因的 HSR/SS 表达比。在存在或不存在应激的情况下，HSR/SS 基因表达的比值几乎没有差异。此外，cFos 表达表明，总体而言，SS 动物的背侧中缝核和穹窿周灰质中的细胞激活低于 HSR 动物。这些数据表明，5-羟色胺系统可能决定个体的敏感性或适应能力，但非人类灵长类动物的 5-羟色胺相关基因表达可能不会对中度压力迅速做出反应。
