Electro-Acupuncture Improve the Early Pattern Separation in Alzheimer's Disease Mice via Basal Forebrain-Hippocampus Cholinergic Neural Circuit.
Electro-Acupuncture Improve the Early Pattern Separation in Alzheimer's Disease Mice via Basal Forebrain-Hippocampus Cholinergic Neural Circuit.
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电针通过基底前脑-海马胆碱能神经回路改善阿尔茨海默病小鼠的早期模式分离
DOI：
10.3389/fnagi.2021.770948
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发表时间：
2021
影响因子：
4.8
通讯作者：
Tao J
中科院分区：
文献类型：
--
作者：
Li L;Li J;Dai Y;Yang M;Liang S;Wang Z;Liu W;Chen L;Tao J
目的：探讨电针对5个家族性突变（5 × FAD）小鼠模式分离的影响及其神经回路机制。电针百会穴和神庭穴各30 min，连续4周。进行认知行为测试以评估电针治疗对认知功能的影响。采用1H-MRS、尼氏染色、免疫组化、免疫荧光等方法检测胆碱能系统的改变。用硫磺素S染色和6 E10免疫荧光法检测β淀粉样蛋白（Aβ）。此外，hM 4Di设计者受体专门激活的设计者药物（DREADDs）病毒和长期氯氮平-N-氧化物注射用于抑制内侧隔和垂直肢的斜角带和齿状回（MS/VDB-DG）胆碱能神经回路。采用认知行为学和免疫荧光技术研究电针改善5 × FAD小鼠认知功能的胆碱能神经回路机制。电针治疗可显著改善5 × FAD小鼠空间识别记忆和图形分离障碍，通过减少神经元丢失、上调胆碱/肌酸、胆碱乙酰转移酶、囊泡乙酰胆碱转运体和下调乙酰胆碱酯酶来调节胆碱能系统。电针治疗后Aβ沉积减少。随后，单突触hM 4Di DREADDs病毒追踪和抑制策略表明，EA处理激活MS/VDB-DG胆碱能神经回路，以改善早期模式分离。此外，电针治疗激活了这一回路，上调M1受体阳性细胞，促进海马齿状回（DG）神经发生。电针可通过激活MS/VDB-DG胆碱能神经回路改善5 × FAD小鼠早期图形分离障碍，这与电针对胆碱能系统的调节和促进神经发生有关。
To explore the effect of electro-acupuncture (EA) treatment on pattern separation and investigate the neural circuit mechanism involved in five familial mutations (5 × FAD) mice. Five familial mutations mice were treated with EA at Baihui (DU20) and Shenting (DU24) acupoints for 30 min each, lasting for 4 weeks. Cognitive-behavioral tests were performed to evaluate the effects of EA treatment on cognitive functions. 1H-MRS, Nissl staining, immunohistochemistry, and immunofluorescence were performed to examine the cholinergic system alteration. Thioflavin S staining and 6E10 immunofluorescence were performed to detect the amyloid-β (Aβ). Furthermore, hM4Di designer receptors exclusively activated by designer drugs (DREADDs) virus and long-term clozapine-N-oxide injection were used to inhibit the medial septal and vertical limb of the diagonal band and dentate gyrus (MS/VDB-DG) cholinergic neural circuit. Cognitive-behavioral tests and immunofluorescence were performed to investigate the cholinergic neural circuit mechanism of EA treatment improving cognition in 5 × FAD mice. Electro-acupuncture treatment significantly improved spatial recognition memory and pattern separation impairment, regulated cholinergic system via reduction neuron loss, upregulation of choline/creatine, choline acetyltransferase, vesicular acetylcholine transporter, and downregulation of enzyme acetylcholinesterase in 5 × FAD mice. Aβ deposition was reduced after EA treatment. Subsequently, the monosynaptic hM4Di DREADDs virus tracing and inhibiting strategy showed that EA treatment activates the MS/VDB-DG cholinergic neural circuit to improve the early pattern separation. In addition, EA treatment activates this circuit to upregulating M1 receptors positive cells and promoting hippocampal neurogenesis in the dentate gyrus (DG). Electro-acupuncture could improve the early pattern separation impairment by activating the MS/VDB-DG cholinergic neural circuit in 5 × FAD mice, which was related to the regulation of the cholinergic system and the promotion of neurogenesis by EA treatment.
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