Study on early cognitive function in transgenic APP/PS-1/tau mice model of Alzheimer's disease

Chinese Journal of Contemporary Neurology and Neurosurgery

Zun-jing LIU¹  Wei-hong GU¹  Li WANG¹  Jin-song JIAO¹  Ryo YAMAMOTO²  Nobuo KATO²  Yuan SHUI³ 

[1] Department of Neurology, China-Japan Friendship Hospital, Beijing 100029, China;Department of Physiology, Kanazawa Medical University, Kanazawa 920-0293, Ishikawa, Japan;Pain Management Center, China-Japan Friendship Hospital, Beijing 100029, China;

关键词: Alzheimer disease;    Cognition disorders;    Synapses;    Amyloid beta-protein;    Disease models, animal;   

DOI  :  

来源: DOAJ

【 摘 要 】

Objective In the present experiment we investigate the behavior of 4-month-old transgenic APP/PS-1/tau mice model with Alzheimer's disease (3 × Tg-AD mice) to evaluate their abilities of spatial learning and memory. We observe the changes of synaptic plasticity and soluble amyloid-β protein 42 (Aβ42) expression in the CA1 region of hippocampus to explore the mechanism of early cognitive impairment of 3 × Tg-AD mice.  Methods Ten 4-month-old male 3 × Tg-AD mice and matched ten 129/C57BL/6 hybrid wild type (WT) mice were enrolled. The open field test and Morris water maze test were conducted to observe emotion disorder and ability of spatial learning and memory. Field excitatory postsynaptic potential (fEPSP) and theta burst stimulation (TBS)-induced long-term potentiation (LTP) were recorded in CA1 region of hippocampus. The expression changes of soluble Aβ42 in hippocampus were measured by enzyme-linked immunosorbent assay (ELISA).  Results The open field test showed that there was no significant differences between 3 × Tg-AD group and control group, which indicated that there was no obvious anxiety tendency in 4-month-old 3 × Tg-AD mice. Compared with control group, 3 × Tg-AD group mice had significantly longer escape latency from the 3rd to 5th day (P = 0.001, 0.003, 0.001) and lower percentage of time through the platform area (P = 0.000). LTP induced by TBS in CA1 region of hippocampus of 3 × Tg-AD group decreased significantly (P < 0.01, for all) compared with that of control group. In contrast to control group, the expression of soluble Aβ42 in the hippocampus of 3 × Tg-AD mice group increased significantly (P = 0.000).  Conclusions The expression of soluble Aβ42 in the hippocampus of 4-month-old 3 × Tg-AD mice increased significantly, which impaired synaptic plasticity in CA1 region of hippocampus and led to a significant decline in spatial learning and memory ability.

 

DOI: 10.3969/j.issn.1672-6731.2015.05.012

【 授权许可】

Unknown