AVP(4-8) Improves Cognitive Behaviors and Hippocampal Synaptic Plasticity in the APP/PS1 Mouse Model of Alzheimer’s Disease  

作　　者：Xiumin Zhang Fang Zhao Chenfang Wang Jun Zhang Yu Bai Fang Zhou Zhaojun Wang Meina Wu Wei Yang Junhong Guo Jinshun Qi 

机构地区：[1]Department of Neurology,First Hospital,Shanxi Medical University,Taiyuan 030001,China [2]Department of Physiology,Key laboratory of Cellular Physiology,Ministry of Education,Shanxi Medical University,Taiyuan 030001,China

出　　处：《Neuroscience Bulletin》2020年第3期254-262,共9页神经科学通报（英文版）

基　　金：the National Natural Science Foundation of China(31471080);the Scientific Program for“Sanjin Scholars”of Shanxi Province,Shanxi“1331 Project”Key Subjects Construction(1331KSC);Science Foundation for Excellent Young Scholars of Shanxi Province,China(201801D211005)。

摘　　要：Memory deficits with aging are related to the neurodegeneration in the brain, including a reduction in arginine vasopressin(AVP) in the brain of patients with Alzheimer’s disease(AD). AVP(4-8), different from its precursor AVP, plays memory enhancement roles in the CNS without peripheral side-effects. However, it is not clear whether AVP(4-8) can improve cognitive behaviors and synaptic plasticity in the APP/PS1 mouse model of AD. Here, we investigated for the first time the neuroprotective effects of AVP(4-8) on memory behaviors and in vivo long-term potentiation(LTP) in APP/PS1-AD mice.The results showed that:(1) APP/PS1-AD mice had lower spontaneous alternation in the Y-maze than wild-type(WT) mice, and this was significantly reversed by AVP(4-8);(2) the prolonged escape latency of APP/PS1-AD mice in the Morris water maze was significantly decreased by AVP(4-8), and the decreased swimming time in target quadrant recovered significantly after AVP(4-8) treatment;(3) in vivo hippocampal LTP induced by high-frequency stimulation had a significant deficit in the AD mice, and this was partly rescued by AVP(4-8);(4) AVP(4-8)significantly up-regulated the expression levels of postsynaptic density 95(PSD95) and nerve growth factor(NGF)in the hippocampus of AD mice. These results reveal the beneficial effects of AVP(4-8) in APP/PS1-AD mice,showing that the intranasal administration of AVP(4-8)effectively improved the working memory and long-term spatial memory of APP/PS1-AD mice, which may be associated with the elevation of PSD95 and NGF levels in the brain and the maintenance of hippocampal synaptic plasticity.

关 键 词：AVP(4-8) APP/PS1 TRANSGENIC mice Cognitive behavior SYNAPTIC plasticity In vivo HIPPOCAMPAL LTP 

分 类 号：R749.16[医药卫生—神经病学与精神病学] R-332[医药卫生—临床医学]