Effects of dopamine transporter changes in the ventral tegmental area of the midbrain on cognitive function in aged rats

J Chem Neuroanat. 2021 Nov:117:102009. doi: 10.1016/j.jchemneu.2021.102009. Epub 2021 Jul 27.

Abstract

The pathogenesis of Perioperative neurocognitive disorders (PND) is a synergistic effect of many factors. Up to now, the exact mechanism remains unclear. The dopamine pathway in the brain is one of the paths involved in the means of cognitive function. Therefore, the purpose of this study was to investigate the relationship between changes in dopamine transporters in the ventral tegmental area (VTA) of the midbrain and postoperative cognitive dysfunction in elderly rats. In this study, a mental dysfunction model in elderly rats was established after splenectomy under general anesthesia. Eighty male SD rats, aged 18-20 months, with a body mass of 300-500 g. Randomly divided into eight groups: Normal group (Normal, N) and Sham group (sham, S), Model 3 day group(PND, P3), Model 7 day group(PND, P7), Virus 3 days AAV·DAT·RNAi (AAV3), Virus 7 days AAV·DAT·RNAi (AAV7), Virus control for three days AAV·NC(NC3), Virus control for seven days AAV·NC(NC7). The results show that knockdown of dopamine transporter in the VTA region can significantly improve the cognitive dysfunction of elderly rats after surgery. These results suggest that dopamine transporter in the VTA region is involved in cognitive dysfunction in elderly rats. The effect of DAT changes in the VTA region on postoperative cognitive function in elderly rats may be related to the regulation of α-syn and Aβ1-42 protein aggregation in the hippocampus.

Keywords: Dopamine transporter; Perioperative neurocognitive disorders; The VTA; The hippocampus; α-synuclein; β-Amyloid1-42.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / metabolism*
  • Amyloid beta-Peptides / analysis
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Cognition / physiology*
  • Dopamine Plasma Membrane Transport Proteins / administration & dosage
  • Dopamine Plasma Membrane Transport Proteins / analysis
  • Dopamine Plasma Membrane Transport Proteins / metabolism*
  • Mesencephalon / chemistry
  • Mesencephalon / metabolism*
  • Peptide Fragments / analysis
  • Peptide Fragments / metabolism
  • RNA, Viral / administration & dosage
  • RNA, Viral / analysis
  • RNA, Viral / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Ventral Tegmental Area / chemistry
  • Ventral Tegmental Area / metabolism*
  • alpha-Synuclein / analysis
  • alpha-Synuclein / metabolism

Substances

  • Amyloid beta-Peptides
  • Dopamine Plasma Membrane Transport Proteins
  • Peptide Fragments
  • RNA, Viral
  • adenovirus associated RNA
  • alpha-Synuclein
  • amyloid beta-protein (1-42)