Mengzhen Zhou, Yaran Li and JiYou Tang*
Background: Decreased AQP 4 expression causes decreased circulatory function of the glymphatic system, and abnormal deposition of proteins such as A β 42 and Tau in the brain. The loss of AQP 4 may be a risk factor for Alzheimer's disease.
Objective: To explore whether TGN-020 (AQP 4 blocker) damages learning and memory, aggravates A β deposition, and whether the combination of DORA and TGN rescues learning and memory impairment in mice.
Methods: During the 28-day intervention period, APP/PS1 mice (AD model mice) received drugs by intraperitoneal injection daily at the start of the light phase (6:00 am). Mouse learning and memory were assessed by the Y and Morris water mazes. After analysis of behavioral parameters, Aβ deposition in the mouse brain was evaluated by immunohistochemistry.
Results: 30 mice (2 died, one in each of TGN + 30 and control groups, mortality of 6.7%) had fewer adverse effects and no significant side effects. For total sleep duration, total sleep duration in APP/PS1 (AD) mice (MD=36717,95%CI: 35807 to 37626) seconds, APP/PS1 (AD) mice (MD=2762,95%CI: 1506 to 4018) seconds, and TGN + APP/PS1 (AD) 30 mice (MD = 16,903,95%CI: 15647 to 18160) seconds. In the Y maze and the Morris water maze, TGN and TGN + 30mg mice had higher escape latency than controls, and A β deposition was increased on immunohistochemistry.
Conclusion: Compared with the control group, the TGN and TGN + 30 groups have impaired learning and memory, and strengthening the Aqp 4-led lymphoid drainage function in the brain has important significance for the generation, development and outcome of Alzheimer's disease. Aqp 4 agonists or AQP 4 open agents are expected to be novel targets for the future treatment of Alzheimer's disease.
