Effects of inosine monophosphate and exercise training on neuronal nitric oxide synthase in the mouse brain
Effects of inosine monophosphate and exercise training on neuronal nitric oxide synthase in the mouse brain
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DOI：
10.1016/j.neulet.2020.135083
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发表时间：
2020-05
影响因子：
2.5
通讯作者：
Yuki Tomiga;Kazuya Sakai;Shihoko Nakashima;Y. Uehara;K. Kawanaka;Y. Higaki
中科院分区：
文献类型：
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作者：
Yuki Tomiga;Kazuya Sakai;Shihoko Nakashima;Y. Uehara;K. Kawanaka;Y. Higaki
最近，嘌呤核苷肌苷已被证明具有多种神经保护作用。同样，运动训练对心理健康和认知功能也有众所周知的有益影响。神经元一氧化氮合酶 (nNOS) 是多个大脑区域的关键神经元信使，nNOS 的下调已被证明可以改善大脑功能。然而，肌苷和运动训练是否对大脑中 nNOS 通路相关蛋白产生联合影响仍不清楚。我们首次发现肌苷单磷酸 (IMP)（肌苷前体）会降低腹侧海马 (vHp) 和小脑 (Ce) 中的 nNOS 水平，但不会降低背侧海马 (dHp) 中的 nNOS 水平。在 vHp 中，cAMP 反应元件结合蛋白 (CREB) 的磷酸化也上调，与 nNOS 蛋白水平呈负相关。在大脑皮层 (Cx) 中，未观察到 nNOS 通路的显着激活。在 dHp、vHp、Cx 和 Ce 中，未观察到 IMP 和运动对 nNOS 蛋白和 CREB 磷酸化水平的影响之间存在相互作用。 nNOS 的磷酸化受磷酸肌醇 3 激酶 (PI3K)/蛋白激酶 B (Akt) 途径的调节。尽管 IMP 引起 Akt 磷酸化的微小变化，但 IMP 或运动均未改变 nNOS 磷酸化。总之，在与情绪行为相关的 vHp 中，IMP 降低了 nNOS 水平并激活了 CREB，表明 IMP 可以引起抗焦虑作用。
Recently, the purine nucleoside inosine has been demonstrated to have several neuroprotective effects. Similarly, exercise training has well-known beneficial effects on mental health and cognitive function. Neuronal nitric oxide synthase (nNOS) is a key neuronal messenger in several brain regions, and the downregulation of nNOS has been shown to improve brain function. However, whether inosine and exercise training have combined effects on nNOS pathway-related proteins in the brain remains unknown. We found, for the first time, that inosine monophosphate (IMP), which is a precursor of inosine, decreases nNOS levels in the ventral hippocampus (vHp) and the cerebellum (Ce), but not in the dorsal hippocampus (dHp). In the vHp, the phosphorylation of cAMP response element-binding protein (CREB) was also upregulated, which negatively correlated with nNOS protein levels. In the cerebral cortex (Cx), no significant activation of the nNOS pathway was observed. In the dHp, vHp, Cx, and Ce, no interactions between the effects of IMP and exercise on nNOS protein and CREB phosphorylation levels were observed. The phosphorylation of nNOS was regulated by the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway. Although IMP induced minor changes in Akt phosphorylation, nNOS phosphorylation was unchanged by either IMP or exercise. In conclusion, in the vHp, which is associated with emotional behavior, IMP decreased nNOS levels and activated CREB, suggesting that IMP can elicit anxiolytic effects.