Minocycline attenuates post-operative cognitive impairment in aged mice by inhibiting microglia activation

J Cell Mol Med. 2016 Sep;20(9):1632-9. doi: 10.1111/jcmm.12854. Epub 2016 Apr 6.

Abstract

Although it is known that isoflurane exposure or surgery leads to post-operative cognitive dysfunction in aged rodents, there are few clinical interventions and treatments available to prevent this disorder. Minocycline (MINO) produces neuroprotection from several neurodegenerative diseases and various experimental animal models. Therefore, we set out to investigate the effects of MINO pre-treatment on isoflurane or surgery induced cognitive impairment in aged mice by assessing the hippocampal-dependent spatial memory performance using the Morris water maze task. Hippocampal tissues were isolated from mice and evaluated by Western blot analysis, immunofluorescence procedures and protein array system. Our results elucidate that MINO down-regulated the isoflurane-induced and surgery-induced enhancement in the protein levels of pro-inflammatory cytokine tumour necrosis factor alpha, interleukin (IL)-1β, interferon-γ and microglia marker Iba-1, and up-regulated protein levels of the anti-inflammatory cytokine IL-4 and IL-10. These findings suggest that pre-treatment with MINO attenuated isoflurane or surgery induced cognitive impairment by inhibiting the overactivation of microglia in aged mice.

Keywords: POCD; isoflurane; microglia; minocycline.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / pathology*
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Appendectomy / adverse effects*
  • Calcium-Binding Proteins / metabolism
  • Cell Count
  • Cognitive Dysfunction / drug therapy*
  • Cognitive Dysfunction / etiology*
  • Cytokines / metabolism
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Inflammation Mediators / metabolism
  • Interleukin-1beta / metabolism
  • Isoflurane / pharmacology
  • Mice
  • Microfilament Proteins / metabolism
  • Microglia / drug effects
  • Microglia / metabolism
  • Microglia / pathology*
  • Minocycline / pharmacology
  • Minocycline / therapeutic use*
  • Spatial Memory / drug effects
  • Up-Regulation / drug effects

Substances

  • Aif1 protein, mouse
  • Anti-Inflammatory Agents
  • Calcium-Binding Proteins
  • Cytokines
  • Inflammation Mediators
  • Interleukin-1beta
  • Microfilament Proteins
  • Isoflurane
  • Minocycline