Yang Miyoung, Ding Qi, Zhang Ming, Moon Changjong, Wang Hongbing
Department of Physiology, Michigan State University, East Lansing, MI, 48824, USA.
Department of Anatomy, Wonkwang University School of Medicine, Iksan, Jeonbuk, 570-749, South Korea.
Neurobiol Stress. 2020 Jun 24;13:100237. doi: 10.1016/j.ynstr.2020.100237. eCollection 2020 Nov.
The ability to cope with stress is essential for emotional stability and mental health. It is also hypothesized that factors promoting resilience to stress may offer treatment strategies for maladaptive disorders such as anxiety and depression. Here, we find that physical restraint reduces the expression of type 1 adenylyl cyclase (), a neurospecific synaptic enzyme that positively regulates the cAMP signaling cascade. Conversely, an increase of forebrain expression in transgenic mouse (i.e., mouse) predisposes individuals to molecular stability and behavioral resilience. Transgenic overexpression of prevents the physical restraint-induced down-regulation of brain-derived neurotrophic factor () and neuropeptide Y (NPY). Further, mice maintain regular locomotive activity in novelty exploration and voluntary wheel running following physical restraint. mice show higher corticosterone and lower basal glucocorticoid receptor (GR) expression, along with a higher MR (mineralocorticoid receptor) to GR ratio in the hippocampus. Further, mice show reduced immobility under acute physical stress conditions in the forced swimming test and are more sensitive to the antidepressant desipramine. Our results demonstrate a novel function of in stress coping and suggest as a potential target to antagonize stress vulnerability and promote antidepressant efficacy.
应对压力的能力对于情绪稳定和心理健康至关重要。还有假说认为，促进抗压能力的因素可能为焦虑和抑郁等适应不良障碍提供治疗策略。在此，我们发现身体束缚会降低1型腺苷酸环化酶（）的表达，该酶是一种神经特异性突触酶，可正向调节环磷酸腺苷（cAMP）信号级联反应。相反，转基因小鼠（即小鼠）前脑表达的增加使个体具有分子稳定性和行为抗压能力。的转基因过表达可防止身体束缚诱导的脑源性神经营养因子（）和神经肽Y（NPY）的下调。此外，小鼠在身体束缚后的新奇探索和自愿轮转运动中保持正常的运动活动。小鼠表现出较高的皮质酮水平和较低的基础糖皮质激素受体（GR）表达，以及海马中较高的盐皮质激素受体（MR）与GR比值。此外，小鼠在强迫游泳试验中急性身体应激条件下的不动时间减少，并且对抗抑郁药地昔帕明更敏感。我们的结果证明了在应对压力方面的新功能，并表明作为对抗压力易感性和提高抗抑郁疗效的潜在靶点。
