Forebrain overexpression of type 1 adenylyl cyclase promotes molecular stability and behavioral resilience to physical stress.
Forebrain overexpression of type 1 adenylyl cyclase promotes molecular stability and behavioral resilience to physical stress.
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前脑 1 型腺苷酸环化酶的过度表达可促进分子稳定性和对身体压力的行为恢复能力。
DOI：
10.1016/j.ynstr.2020.100237
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发表时间：
2020-11
影响因子：
5
通讯作者：
Wang H
中科院分区：
文献类型：
--
作者：
Yang M;Ding Q;Zhang M;Moon C;Wang H
应对压力的能力对于情绪稳定和心理健康至关重要。还假设，促进压力恢复能力的因素可能为焦虑和抑郁等适应不良性疾病提供治疗策略。在这里，我们发现身体束缚会降低 1 型腺苷酸环化酶 (Adcy1) 的表达，这是一种神经特异性突触酶，可正向调节 cAMP 信号级联。相反，转基因小鼠（即 Adcy1tg 小鼠）前脑 Adcy1 表达的增加使个体倾向于分子稳定性和行为弹性。 Adcy1 的转基因过表达可防止身体约束引起的脑源性神经营养因子 (BDNF) 和神经肽 Y (NPY) 的下调。此外，Adcy1tg 小鼠在新奇探索和身体约束后的自愿轮跑中保持规律的运动活动。 Adcy1tg 小鼠表现出较高的皮质酮和较低的基础糖皮质激素受体 (GR) 表达，以及较高的海马 MR（盐皮质激素受体）与 GR 比率。此外，Adcy1tg 小鼠在强迫游泳测试中在急性身体应激条件下表现出不动性减少，并且对抗抑郁药地昔帕明更敏感。我们的结果证明了 Adcy1 在压力应对中的新功能，并表明 Adcy1 作为对抗压力脆弱性和提高抗抑郁功效的潜在靶点。
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 (Adcy1), a neurospecific synaptic enzyme that positively regulates the cAMP signaling cascade. Conversely, an increase of forebrain Adcy1 expression in transgenic mouse (i.e., Adcy1tg mouse) predisposes individuals to molecular stability and behavioral resilience. Transgenic overexpression of Adcy1 prevents the physical restraint-induced down-regulation of brain-derived neurotrophic factor (BDNF) and neuropeptide Y (NPY). Further, Adcy1tg mice maintain regular locomotive activity in novelty exploration and voluntary wheel running following physical restraint. Adcy1tg 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, Adcy1tg 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 Adcy1 in stress coping and suggest Adcy1 as a potential target to antagonize stress vulnerability and promote antidepressant efficacy.
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影响因子：
4.2
作者：
Kim, Kyoung-Shim;Han, Pyung-Lim
通讯作者：
Han, Pyung-Lim
影响因子：
10.6
作者：
Duman, Catharine H.;Schlesinger, Lee;Duman, Ronald S.
通讯作者：
Duman, Ronald S.
影响因子：
4.7
作者：
Cantone M;Bramanti A;Lanza G;Pennisi M;Bramanti P;Pennisi G;Bella R
通讯作者：
Bella R
记忆的分子生物学：cAMP、PKA、CRE、CREB-1、CREB-2 和 CPEB。
影响因子：
3.6
作者：
Kandel ER
通讯作者：
Kandel ER
影响因子：
4.7
作者：
Dowlatshahi, D;MacQueen, GM;Young, LT
通讯作者：
Young, LT