Kim Sarah, Gacek Stephanie A, Mocchi Madaline M, Redei Eva E
Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States.
Front Behav Neurosci. 2021 Dec 14;15:779036. doi: 10.3389/fnbeh.2021.779036. eCollection 2021.
Genetic predisposition and environmental stress are known etiologies of stress-related psychiatric disorders. Environmental stress during adolescence is assumed to be particularly detrimental for adult affective behaviors. To investigate how genetic stress-reactivity differences modify the effects of stress during adolescence on adult affective behaviors we employed two inbred strains with differing stress reactivity. The Wistar Kyoto More Immobile (WMI) rat strain show increased stress-reactivity and despair-like behaviors as well as passive coping compared to the nearly isogenic control strain, the Wistar Kyoto Less Immobile (WLI). Males and females of these strains were exposed to contextual fear conditioning (CFC) during early adolescence (EA), between 32 and 34 postnatal days (PND), and were tested for the consequences of this mild EA stress in adulthood. Early adolescent stress significantly decreased anxiety-like behavior, measured in the open field test (OFT) and increased social interaction and recognition in adult males of both strains compared to controls. In contrast, no significant effects of EA stress were observed in adult females in these behaviors. Both males and females of the genetically less stress-reactive WLI strain showed significantly increased immobility in the forced swim test (FST) after EA stress compared to controls. In contrast, immobility was significantly attenuated by EA stress in adult WMI females compared to controls. Transcriptomic changes of the glucocorticoid receptor (, GR) and the brain-derived neurotrophic factor () illuminate primarily strain and stress-dependent changes, respectively, in the prefrontal cortex and hippocampus of adults. These results suggest that contrary to expectations, limited adolescent stress is beneficial to males thru decreasing anxiety and enhancing social behaviors, and to the stress more-reactive WMI females by way of decreasing passive coping.
遗传易感性和环境压力是与压力相关的精神疾病的已知病因。青春期的环境压力被认为对成年后的情感行为特别有害。为了研究遗传应激反应差异如何改变青春期压力对成年情感行为的影响，我们使用了两种应激反应不同的近交系。与近等基因对照品系Wistar Kyoto Less Immobile（WLI）相比，Wistar Kyoto More Immobile（WMI）大鼠品系表现出更高的应激反应、绝望样行为以及被动应对方式。这些品系的雄性和雌性在青春期早期（EA），即出生后32至34天（PND），接受情境恐惧条件反射（CFC），并测试这种轻度EA应激在成年期的后果。与对照组相比，青春期早期应激显著降低了旷场试验（OFT）中测量的焦虑样行为，并增加了两个品系成年雄性的社交互动和识别能力。相比之下，在这些行为中未观察到EA应激对成年雌性有显著影响。与对照组相比，遗传应激反应较低的WLI品系的雄性和雌性在EA应激后强迫游泳试验（FST）中的不动时间显著增加。相比之下，与对照组相比，成年WMI雌性在EA应激后不动时间显著减少。糖皮质激素受体（GR）和脑源性神经营养因子（BDNF）的转录组变化分别主要揭示了成年前额叶皮质和海马体中品系和应激依赖性变化。这些结果表明，与预期相反，有限的青春期应激通过降低焦虑和增强社交行为对雄性有益，并通过减少被动应对方式对应激反应更强的WMI雌性有益。
