Open AccessIntranasal insulin alleviates cognitive deficits and amyloid pathology in young adult APP swe/ PS 1dE9 mice
Author(s) -
Mao YanFang,
Guo Zhangyu,
Zheng Tingting,
Jiang Yasi,
Yan Yaping,
Yin Xinzhen,
Chen Yanxing,
Zhang Baorong
Publication year - 2016
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12498
Subject(s) - nasal administration , insulin , hippocampal formation , neurogenesis , insulin degrading enzyme , amyloid precursor protein , insulin receptor , amyloid (mycology) , endocrinology , alzheimer's disease , insulin resistance , medicine , biology , pharmacology , neuroscience , disease , pathology
Summary Brain insulin signaling deficits contribute to multiple pathological features of Alzheimer's disease ( AD ). Although intranasal insulin has shown efficacy in patients with AD , the underlying mechanisms remain largely unillustrated. Here, we demonstrate that intranasal insulin improves cognitive deficits, ameliorates defective brain insulin signaling, and strongly reduces β‐amyloid (Aβ) production and plaque formation after 6 weeks of treatment in 4.5‐month‐old APP swe/ PS 1dE9 ( APP / PS 1) mice. Furthermore, c‐Jun N‐terminal kinase activation, which plays a pivotal role in insulin resistance and AD pathologies, is significantly inhibited. The alleviation of amyloid pathology by intranasal insulin results mainly from enhanced nonamyloidogenic processing and compromised amyloidogenic processing of amyloid precursor protein ( APP ), and from a reduction in apolipoprotein E protein which is involved in Aβ metabolism. In addition, intranasal insulin effectively promotes hippocampal neurogenesis in APP / PS 1 mice. This study, exploring the mechanisms underlying the beneficial effects of intranasal insulin on Aβ pathologies in vivo for the first time, highlights important preclinical evidence that intranasal insulin is potentially an effective therapeutic method for the prevention and treatment of AD .