Prelimbic Cortical Stimulation Improves Spatial Memory Through Distinct Patterns of Hippocampal Gene Expression in Aged Rats

Shawn Zheng Kai Tan, Joveen Neoh, Andrew John Lawrence, Ed Xuekui Wu, Lee Wei Lim*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

Dementia poses major health challenges worldwide, yet current treatments are faced with issues of efficacy and toxicity. Deep brain stimulation (DBS) is a promising non-pharmacological treatment for dementia, but most DBS studies use young healthy animals, which may not be aetiologically relevant. In this study, we used an aged rat model in which cognitive decline occurs through a natural ageing process. We used a Morris water maze (MWM) to determine the effects of prelimbic cortex (PrL) DBS on memory in aged rats. To investigate the underlying mechanisms of the effects of DBS, we carried out microarray, quantitative PCR analysis, and mass spectrometry to detect gene expression and neurotransmitter changes in the hippocampus. We showed PrL DBS improved the performance in MWM, with related distinct patterns of gene expression involving G protein–coupled receptor pathways. We further found neurotransmitter changes in the dorsal hippocampus, which corroborated and extended the microarray findings. Our results suggest that non-neurogenesis pathways play roles in the effects of DBS. Further studies are needed to investigate the effects of DBS on memory beyond neurogenesis and to consider the highlighted pathways suggested by our data.

Original languageEnglish
Pages (from-to)2054-2068
Number of pages15
JournalNeurotherapeutics
Volume17
Issue number4
DOIs
Publication statusPublished - Oct 2020
Externally publishedYes

Keywords

  • Deep brain stimulation
  • dementia
  • hippocampus
  • memory
  • microarray
  • prelimbic cortex

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