Gene delivery of Homer1c rescues spatial learning in a rodent model of cognitive aging

  • Gerstein H
  • Lindstrom M
  • Burger C
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Abstract

Homer1c has been shown to play a role in learning and memory. Overexpression of Homer1c in the hippocampus can improve memory in normal rats and can also rescue spatial learning deficits in Homer1 knockout mice. In a previous study, we found that Homer1c mRNA is upregulated after a spatial learning paradigm in aged rats that successfully learn the task, when compared to aged rats that are learning-impaired (AI). This study was designed to validate the role of Homer1c in successful cognitive aging. In this article, we report that gene delivery of Homer1c into the hippocampus of aged learning-impaired rats significantly improves individual performance on an object location memory task. The learning ability of these rats on the Morris Water Maze was also superior to that of AI control rats. In summary, using 2 independent spatial memory tasks, we demonstrate that Homer1c is sufficient to improve the spatial learning deficits in a rodent model of cognitive aging. These results point to Homer1c as a potential therapeutic target for improving age-related cognitive impairment.

Author-supplied keywords

  • Aging/*genetics/*psychology
  • Animals
  • Carrier Proteins/*genetics/*physiology
  • Disease Models, Animal
  • Gene Expression
  • Gene Transfer Techniques
  • Genetic Therapy/methods
  • Hippocampus/physiology
  • Homer Scaffolding Proteins
  • Male
  • Maze Learning/*physiology
  • Memory Disorders/*genetics/*psychology/therapy
  • Mice
  • Molecular Targeted Therapy
  • RNA, Messenger/metabolism
  • Rats
  • Rats, Inbred F344
  • Spatial Behavior/*physiology
  • Up-Regulation

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Authors

  • H Gerstein

  • M J Lindstrom

  • C Burger

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