The Second Affiliated Hospital of Hainan Medical University, Department of Neurology, Haikou, Hainan 570216, China; Hainan Provincial Key Laboratory of Tropical Brain Research and Transformation, Hainan 571199, China; International Center for Aging and Cancer (ICAC), Hainan Medical University, Hainan 571199, China.
The First Affiliated Hospital, Department of Neurosurgery, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China.
Peptides. 2022 Oct;156:170847. doi: 10.1016/j.peptides.2022.170847. Epub 2022 Jul 28.
Chronic stress induces neuronal death and impairs hippocampal neurogenesis, thus leading to cognitive deficits and depressive-like behaviors. Our previous studies found that apelin-13, a novel neuropeptide, and its receptors can improve cognitive impairment and depressive-like behaviors in rats, but its mechanism remains unknown. The study aims to evaluate the underlying mechanism of apelin-13 on cognitive impairment and depressive-like behaviors. A 4-week chronic unpredictable mild stress (CUMS) is used to establish a rat model of depression. Apelin-13(2 ug/day) is administered daily to the rats during the last 1 week. Depressive-like behaviors, including tail suspension test (TST) and sucrose preference test (SPT), are performed. The cognitive functions are established by identify index of novel objects recognition test (NORT) and the number of crossing hidden platform in morris water maze (MWM). The neuronal death is measured by popidium iodide (PI) and flow cytometry. The activity of superoxide dismutase (SOD) and glutathione-peroxidase (GSH-PX) in the hippocampus are determined. The protein expressions of p-AMPK, AMPK, BDNF, FNDC5 and PGC-1α are examined. Golgi staining observed the spine dendritic arborization of the hippocampal cornu ammonis 1 (CA1) subregion. Results showed that apelin-13 improves cognitive impairment and ameliorates depressive-like behaviors. Moreover, apelin-13 significantly inhibits neuronal death via AMPK/PGC-1α/FNDC5/BDNF pathway. Taken together, apelin-13 could exert antidepressant effects via protecting neuron functions, which might be related to the activation of AMPK/PGC-1α/FNDC5/BDNF pathway.
慢性应激会导致神经元死亡，并损害海马神经发生，从而导致认知缺陷和类似抑郁的行为。我们之前的研究发现，apelin-13 是一种新型神经肽，其受体可以改善大鼠的认知障碍和类似抑郁的行为，但具体机制尚不清楚。本研究旨在评估 apelin-13 对认知障碍和类似抑郁行为的潜在作用机制。采用为期 4 周的慢性不可预测轻度应激（CUMS）建立大鼠抑郁模型。在最后 1 周，每天给大鼠给予 apelin-13（2ug/天）。进行行为学测试，包括悬尾实验（TST）和蔗糖偏好实验（SPT），以评估大鼠的抑郁样行为；通过新物体识别实验（NORT）和 Morris 水迷宫实验（MWM）中的穿越隐藏平台次数来评估大鼠的认知功能；通过碘化丙啶（PI）和流式细胞术检测神经元死亡；测定海马中超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH-PX）的活性；检测海马中 p-AMPK、AMPK、BDNF、FNDC5 和 PGC-1α 的蛋白表达；利用 Golgi 染色观察海马 CA1 区树突分支的形态。结果表明，apelin-13 改善了认知障碍，缓解了类似抑郁的行为。此外，apelin-13 通过 AMPK/PGC-1α/FNDC5/BDNF 通路显著抑制神经元死亡。综上，apelin-13 通过保护神经元功能发挥抗抑郁作用，其机制可能与激活 AMPK/PGC-1α/FNDC5/BDNF 通路有关。
