Enhancement of beta-amyloid oligomer accumulation after intracerebroventricular injection of streptozotocin, which involves central insulin signaling in a transgenic mouse model
机构：[a]Department of Neurology, Xuan Wu Hospital, Capital Medical University,,Beijing, China神经内科首都医科大学宣武医院[b]Center of Alzheimer’s Disease, Beijing Institute for Brain Disorders,,Beijing, China[c]Beijing Key Laboratory of Geriatric Cognitive Disorders,,Beijing, China[d]Key Neurodegenerative Laboratory of Ministry of Education of the People’s Republic of China,Beijing, China
The beta-amyloid (A beta) oligomer rather than fibrillar A beta has become the important focus of recent studies on the pathogenesis of Alzheimer's disease (AD). Insulin signaling plays important roles in cognitive disease, such as AD. However, in-vivo evidence for the link between central insulin signaling and the A beta oligomer are lacking, and the mechanisms underlying the effect of central insulin signaling on AD are still elusive. Our team has established the Presenilin-1 Val97Leu mutant transgenic (PS1(V97L)) AD mouse model with the intraneuronal A beta oligomer as the potential initiator for other pathologies, but without extracellular amyloid plaque formation. Using this model, we investigated the roles of disturbed central insulin signaling induced by intracerebroventricular injection of streptozotocin (STZ) in the progression of AD. We observed that PS1(V97L) mice after intracerebroventricular injection of STZ showed increased A beta oligomer accumulation and aggravated spatial learning and memory deficit in the absence of diabetes symptoms. Furthermore, STZ administration inhibited the activation of the insulin receptor and enhanced the activation of c-Jun NH2-terminal kinase, which was accompanied by increased production of carboxy-terminal fragments from the amyloid precursor protein, in the brain of PS1(V97L) mice. Overall, our study provided in-vivo evidence for a role of central insulin signaling in AD progression. (c) 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins.
基金：
China–Canada Joint Initiative on Alzheimer’s Disease and Related Disorders(812111340)
the key project of the National Natural Science Foundation of China (30830045).
第一作者机构：[a]Department of Neurology, Xuan Wu Hospital, Capital Medical University,,Beijing, China
通讯作者：
通讯机构：[*1]Xuan Wu Hospital, Capital Medical University, 45 Changchun Street, Beijing 100053, China
推荐引用方式(GB/T 7714)：
Fangju Lin,Jianping Jia,Wei Qin.Enhancement of beta-amyloid oligomer accumulation after intracerebroventricular injection of streptozotocin, which involves central insulin signaling in a transgenic mouse model[J].NEUROREPORT.2014,25(16):1289-1295.doi:10.1097/WNR.0000000000000261.
APA：
Fangju Lin,Jianping Jia&Wei Qin.(2014).Enhancement of beta-amyloid oligomer accumulation after intracerebroventricular injection of streptozotocin, which involves central insulin signaling in a transgenic mouse model.NEUROREPORT,25,(16)
MLA：
Fangju Lin,et al."Enhancement of beta-amyloid oligomer accumulation after intracerebroventricular injection of streptozotocin, which involves central insulin signaling in a transgenic mouse model".NEUROREPORT 25..16(2014):1289-1295
