Activation of the RMTg Nucleus by Chemogenetic Techniques Alleviates the Learning and Memory Impairment in APP/PS1 Mice

Ling Zheng,1– 3 Zhenjie Wang,2 Yujia Liu,4 Jiapei Zhao,5 Saie Huang1,3 1Rehabilitation Hospital Affiliated to Fujian University of Traditional Chinese Medicine, Fuzhou, People’s Republic of China; 2College of Rehabilitation Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, People’s Republic of China; 3Fujian Key Laboratory of Rehabilitation Technology, Fuzhou, People’s Republic of China; 4College of Traditional Chinese Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, People’s Republic of China; 5Department of Rehabilitation Medicine, Xiamen Fifth Hospital, Xiamen, People’s Republic of ChinaCorrespondence: Saie Huang, Email saiehuang@fjtcm.edu.cnObjective: There is a relationship between non-rapid eye movement (NREM) sleep and Alzheimer’s disease (AD). The rostromedial tegmental nucleus (RMTg) is activated can enhance NREM. Therefore, our experiment was designed to investigate the effects of activation of RMTg by chemical genetic techniques on APP/PS1 mice learning and memory.Materials and Methods: After the AAV-hSyn-hM3Dq-mCherry virus was injected into the RMTg nucleus, CNO solution was intraperitoneally injected to activate RMTg. The new object test and Morris water maze were used to determine the learning and memory level; T2-weighted imaging (T2WI) scanning was performed to analyze the volume of hippocampus and entorhinal cortex of each group; The virus transfection status was determined by laser confocal microscope and use immunohistochemical detection to observe the deposition of Beta Amyloid 1– 42 (Aβ 42).Results: Activation of RMTg by chemical genetic techniques can reduce the escape latency and increase discrimination index (RI) and the number of crossing platform; Activation of RMTg by chemical genetic techniques reduced the atrophy of the entorhinal cortex. Aβ 42 deposition in the brain was decreased after activation of RMTg.Conclusion: Activation of the RMTg nucleus by chemogenetic techniques can improve the learning and memory impairment in APP/PS1 mice.Keywords: Alzheimer’s disease, chemical genetics, rostromedial tegmental nucleus, RMTg, learning and memory, amyloid-β, Aβ