Xi'an Medical University School of Nursing, Xi'an, Shaanxi, PR China.
Northwest Women and Children Hospital, Xi'an, Shaanxi, PR China.
Behav Brain Funct. 2021 Apr 16;17(1):2. doi: 10.1186/s12993-021-00175-z.
Middle-aged females, especially perimenopausal females, are vulnerable to depression, but the potential mechanism remains unclear. Dopaminergic and GABAergic system dysfunction is involved in the pathophysiology of depression. In the current study, we used 2-month-old and 11-month-old C57BL/6 mice as young and middle-aged mice, respectively. Chronic immobilization stress (CIS) was used to induce depressive-like behaviour, and the sucrose preference test (SPT), tail suspension test (TST) and forced swim test (FST) were used to assess these behaviours. We then measured the mRNA levels of dopamine receptor D1 (DRD1) and the GABA receptors GABRA1, GABRB2 and GABRG2 in the nucleus accumbens (NAc) and prefrontal cortex (PFC).
We found that immobility time in the FST was significantly increased in the middle-aged mice compared with the middle-aged control mice and the young mice. In addition, the preference for sucrose water was reduced in the middle-aged mice compared with the middle-aged control mice. However, CIS did not induce obvious changes in the performance of the young mice in our behavioural tests. Moreover, the middle-aged mice exhibited equal immobility times as the young mice in the absence of stress. Decreases in the mRNA levels of DRD1, GABRA1, and GABRB2 but not GABRG2 were found in the NAc and PFC in the middle-aged mice in the absence of stress. Further decreases in the mRNA levels of DRD1 in the NAc and GABRG2 in the NAc and PFC were found in the middle-aged mice subjected to CIS.
Our results suggested that ageing could not directly induce depression in the absence of stress. However, ageing could induce susceptibility to depression in middle-aged mice in the presence of stress. CIS-induced decreases in DRD1 and GABRG2 levels might be involved in the increase in susceptibility to depression in this context.
中年女性，尤其是围绝经期女性，易患抑郁症，但潜在机制尚不清楚。多巴胺能和 GABA 能系统功能障碍与抑郁症的病理生理学有关。在本研究中，我们分别使用 2 个月大和 11 个月大的 C57BL/6 小鼠作为年轻和中年小鼠。采用慢性束缚应激（CIS）诱导抑郁样行为，蔗糖偏好试验（SPT）、悬尾试验（TST）和强迫游泳试验（FST）评估这些行为。然后，我们测量了伏隔核（NAc）和前额叶皮层（PFC）中多巴胺受体 D1（DRD1）和 GABA 受体 GABRA1、GABRB2 和 GABRG2 的 mRNA 水平。
我们发现，与中年对照组和年轻组相比，中年组在 FST 中的不动时间明显增加。此外，与中年对照组相比，中年组对糖水的偏好降低。然而，CIS 并未在我们的行为测试中引起年轻组的明显变化。此外，在没有应激的情况下，中年组的不动时间与年轻组相等。在没有应激的情况下，中年组在 NAc 和 PFC 中发现 DRD1、GABRA1 和 GABRB2 的 mRNA 水平降低，但 GABRG2 除外。在 CIS 处理的中年小鼠中，NAc 中的 DRD1 和 NAc 和 PFC 中的 GABRG2 的 mRNA 水平进一步降低。
我们的结果表明，在没有应激的情况下，衰老本身不能直接导致抑郁。然而，衰老可能会导致应激状态下中年小鼠易患抑郁症。CIS 诱导的 DRD1 和 GABRG2 水平降低可能与这种情况下易感性增加有关。
