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Impairment of insulin receptor substrate 1 signaling by insulin resistance inhibits neurite outgrowth and aggravates neuronal cell death

Authors
 J. Song  ;  S.M. Kang  ;  E. Kim  ;  C.-H. Kim  ;  H.-T. Song  ;  J.E. Lee 
Citation
 Neuroscience, Vol.301 : 26-38, 2015 
Journal Title
 Neuroscience 
ISSN
 0306-4522 
Issue Date
2015
Abstract
In the central nervous system (CNS), insulin resistance (I/R) can cause defective neurite outgrowth and neuronal cell death, which can eventually lead to cognitive deficits. Recent research has focused on the relationship between I/R and the cognitive impairment caused by dementia, with the goal of developing treatments for dementia. Insulin signal transduction mediated by insulin receptor substrate (IRS-1) has been thoroughly studied in the CNS of patients with I/R. In the present study, we investigated whether the impairment of IRS-1-mediated insulin signaling contributes to neurite outgrowth and neuronal loss, both in mice fed a high-fat diet and in mouse neuroblastoma (Neuro2A) cells. To investigate the changes caused by the inhibition of IRS-1-mediated insulin signaling in the brain, we performed Cresyl Violet staining and immunochemical analysis. To investigate the changes caused by the inhibition of IRS-1-mediated insulin signaling in neuroblastoma cells, we performed Western blot analysis, reverse transcription-PCR, and immunochemical analysis. We show that the deactivation of IRS-1-mediated insulin signaling can inhibit neuronal outgrowth and aggravate neuronal cell death in the insulin-resistant CNS. Thus, IRS-1-mediated insulin signal transduction may be an important factor in the treatment of cognitive decline induced by I/R.
Full Text
http://www.sciencedirect.com/science/article/pii/S0306452215005230
DOI
10.1016/j.neuroscience.2015.05.072
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Radiology (영상의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Psychiatry (정신과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Anatomy (해부학교실) > 1. Journal Papers
Yonsei Authors
김어수(Kim, Eosu) ORCID logo https://orcid.org/0000-0001-9472-9465
김철훈(Kim, Chul Hoon) ORCID logo https://orcid.org/0000-0002-7360-429X
송주현(Song, Ju Hyun)
송호택(Song, Ho Taek) ORCID logo https://orcid.org/0000-0002-6655-2575
이종은(Lee, Jong Eun) ORCID logo https://orcid.org/0000-0001-6203-7413
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/140317
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