Chronic treatment with anesthetic propofol improves cognitive function and attenuates caspase activation in both aged and Alzheimer's disease transgenic mice

Haijun Shao, Yiying Zhang, Yuanlin Dong, Buwei Yu, Weiming Xia, Zhongcong Xie

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

There is a need to seek new treatment(s) for Alzheimer's disease (AD). A recent study showed that AD patients may have decreased levels of functional GABA receptors. Propofol, a commonly used anesthetic, is a GABA receptor agonist. We therefore set out to perform a proof of concept study to determine whether chronic treatment with propofol (50 mg/kg/week) can improve cognitive function in both aged wild-type (WT) and AD transgenic (Tg) mice. Propofol was administrated to the WT and AD Tg mice once a week for 8 or 12 weeks, respectively. Morris water maze was used to assess the cognitive function of the mice following the propofol treatment. Activation of caspase-3, caspase-9, and caspase-8 was investigated using western blot analysis at the end of the propofol treatment. In the mechanistic studies, effects of propofol, amyloid-? protein (A?), and GABA receptor antagonist flumazenil on caspase-3 activation and opening of the mitochondrial permeability transition pore were assessed in H4 human neuroglioma and mouse neuroblastoma cells by western blot analysis and flow cytometry. Here we showed that the propofol treatment improved cognitive function and attenuated brain caspase-3 and caspase-9 activation in both aged WT and AD Tg mice. Propofol attenuated A?-induced caspase-3 activation and opening of the mitochondrial permeability transition pore in the cells, and flumazenil inhibited the propofol's effects. These results suggested that propofol might improve cognitive function via attenuating the A?-induced mitochondria dysfunction and caspase activation, which explored the potential that anesthetic propofol could improve cognitive function in elderly and AD patients.

Original languageEnglish (US)
Pages (from-to)499-513
Number of pages15
JournalJournal of Alzheimer's Disease
Volume41
Issue number2
DOIs
StatePublished - Jan 1 2014

Keywords

  • Aging
  • Alzheimer's disease
  • Amyloid-? protein
  • Anesthesia
  • Apoptosis
  • Mitochondria
  • Neurodegeneration
  • Propofol

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

Fingerprint Dive into the research topics of 'Chronic treatment with anesthetic propofol improves cognitive function and attenuates caspase activation in both aged and Alzheimer's disease transgenic mice'. Together they form a unique fingerprint.

Cite this