Electroacupuncture Enhances Neuroplasticity by Regulating the Orexin A-Mediated cAMP/PKA/CREB Signaling Pathway in Senescence-Accelerated Mouse Prone 8 (SAMP8) Mice.

Electroacupuncture Enhances Neuroplasticity by Regulating the Orexin A-Mediated cAMP/PKA/CREB Signaling Pathway in Senescence-Accelerated Mouse Prone 8 (SAMP8) Mice.
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电针通过调节衰老加速小鼠 pron 8 (SAMP8) 小鼠中食欲素 A 介导的 cAMP/PKA/CREB ​​信号通路增强神经可塑性

DOI:
10.1155/2022/8694462
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发表时间:
2022
影响因子:
--
通讯作者:
Shang H
Shang H
中科院分区:
生物学2区
文献类型:
--
作者:
Hou Z;Yang X;Li Y;Chen J;Shang H

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学习记忆障碍和神经可塑性下降是年龄引起的认知功能障碍的主要临床表现。据报道,食欲素 A (OxA) 在阿尔茨海默病 (AD) 患者的脑脊液 (CSF) 中表达异常升高,并与认知障碍相关。在这里,我们进一步评估了兴奋性神经递质 OxA 是否参与衰老加速小鼠 pron 8 (SAMP8) 小鼠的神经可塑性和认知功能。在本研究中,我们通过行为测试、脑脊液微透析、免疫荧光、甲苯胺蓝染色、基因沉默、透射电子显微镜和蛋白质印迹研究了OxA的机制。结果表明,10Hz电针(EA)有效缓解7月龄SAMP8小鼠学习记忆障碍,降低脑脊液中OxA水平,升高神经递质谷氨酸水平,减轻海马组织病理损伤,改善突触结构,增强突触传递,调节cAMP/PKA/CREB信号通路相关蛋白的表达。这些结果表明,EA通过调节OxA介导的cAMP/PKA/CREB信号通路增强SAMP8小鼠的神经可塑性,从而改善认知功能。这些发现表明,电针可能有益于预防和治疗年龄引起的认知障碍。
Learning and memory disorders and decreased neuroplasticity are the main clinical manifestations of age-induced cognitive dysfunction. Orexin A (OxA) has been reported to show abnormally elevated expression in the cerebrospinal fluid (CSF) of patients with Alzheimer's disease (AD) and to be associated with cognitive impairment. Here, we further assessed whether the excitatory neurotransmitter OxA is involved in neuroplasticity and cognitive function in senescence-accelerated mouse prone 8 (SAMP8) mice. In this study, we investigated the mechanism of OxA by using behavioral tests, CSF microdialysis, immunofluorescence, toluidine blue staining, gene silencing, transmission electron microscopy, and Western blotting. The results showed that 10 Hz electroacupuncture (EA) effectively alleviated learning and memory impairment in 7-month-old SAMP8 mice, reduced OxA levels in the CSF, increased the level of the neurotransmitter glutamate, alleviated pathological damage to hippocampal tissue, improved the synaptic structure, enhanced synaptic transmission, and regulated the expression of cAMP/PKA/CREB signaling pathway-related proteins. These results suggest that EA enhances neuroplasticity in SAMP8 mice by regulating the OxA-mediated cAMP/PKA/CREB signaling pathway, thus improving cognitive function. These findings suggest that EA may be beneficial for the prevention and treatment of age-induced cognitive impairment.