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

 J. Song  ;  S.M. Kang  ;  E. Kim  ;  C.-H. Kim  ;  H.-T. Song  ;  J.E. Lee 
 NEUROSCIENCE, Vol.301 : 26-38, 2015 
Journal Title
Issue Date
Animals ; Apoptosis* ; Brain/metabolism* ; Brain/pathology ; Cell Line, Tumor ; Diet, High-Fat ; Forkhead Box Protein O3 ; Forkhead Transcription Factors/metabolism ; Insulin Receptor Substrate Proteins/metabolism* ; Insulin Resistance* ; Male ; Mice ; Mice, Inbred ICR ; Neurites/metabolism ; Neurons/metabolism* ; Neurons/pathology ; Oncogene Protein v-akt/metabolism ; Phosphorylation ; Reactive Oxygen Species ; Signal Transduction
high-fat diet (HFD) animal model ; insulin receptor substrate 1 (IRS-1) ; insulin resistance ; neurite outgrowth ; neuronal cell death
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.
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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
Kim, Eosu(김어수) ORCID logo https://orcid.org/0000-0001-9472-9465
Kim, Chul Hoon(김철훈) ORCID logo https://orcid.org/0000-0002-7360-429X
Song, Ju Hyun(송주현)
Song, Ho Taek(송호택) ORCID logo https://orcid.org/0000-0002-6655-2575
Lee, Jong Eun(이종은) ORCID logo https://orcid.org/0000-0001-6203-7413
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