Down-regulation of IGF-1/IGF-1R in hippocampus of rats with vascular dementia

Neurosci Lett. 2012 Mar 28;513(1):20-4. doi: 10.1016/j.neulet.2012.01.077. Epub 2012 Feb 10.

Abstract

Insulin-like growth factor-1 (IGF-1) has been demonstrated to have neuroprotective effects, but little is known concerning its role in vascular dementia (VaD). This study aimed to evaluate expression of IGF-1 signaling in hippocampus in rat model of VaD, and probe the underlying mechanisms. Permanent occlusion of bilateral common carotid arteries (2-VO) was used as VaD model. Learning and memory functions were declined significantly in 2-VO rats, and these impairments were further deteriorated with the prolongation of 2-VO treatment. IGF-1, IGF-1 receptor (IGF-1R), total Akt and phosphorylated Akt (p-Akt) were all measured at 1, 2 and 4 months following 2-VO injury. Compared with controls, IGF-1, IGF-1 mRNA and p-Akt expression were significantly decreased in hippocampus of 2-VO rats. However, changes of IGF-1R and total Akt levels were not significant. These results suggest that down-regulation of IGF-1 and p-Akt may contribute to the impairments of learning and memory functions after 2-VO. IGF-1/IGF-1R signaling system may involved in the onset and development of VaD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Carotid Artery, Common / physiology
  • Dementia, Vascular / metabolism*
  • Dementia, Vascular / psychology
  • Down-Regulation / physiology
  • Enzyme-Linked Immunosorbent Assay
  • Hippocampus / metabolism*
  • Insulin-Like Growth Factor I / biosynthesis*
  • Male
  • Maze Learning / physiology
  • Memory / physiology
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Real-Time Polymerase Chain Reaction
  • Receptor, IGF Type 1 / biosynthesis*

Substances

  • RNA, Messenger
  • Insulin-Like Growth Factor I
  • Receptor, IGF Type 1
  • Proto-Oncogene Proteins c-akt