Quetiapine prevents oligodendrocyte and myelin loss and promotes maturation of oligodendrocyte progenitors in the hippocampus of global cerebral ischemia mice

J Neurochem. 2012 Oct;123(1):14-20. doi: 10.1111/j.1471-4159.2012.07883.x. Epub 2012 Aug 14.

Abstract

White matter impairment is a feature of vascular depression. The anti-psychotic quetiapine has been shown to enhance the therapeutic effects of anti-depressants on vascular depression, but the mechanism remains unknown. In this study, we found that 2 weeks of treatment with quetiapine prior to bilateral carotid artery occlusion and reperfusion, in an animal model of vascular depression, resulted in reduced myelin breakdown and oligodendrocyte loss compared to placebo-treated mice on post-operative day (POD) 7. For late stage of recovery (POD40), quetiapine treatment resulted in enhanced oligodendrocyte maturation relative to placebo. The results suggest that quetiapine is a potential intervention for oligodendrocyte damage and this may contribute to its anti-depressant effects through white matter protection in vascular depression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Antigens / metabolism
  • Antipsychotic Agents / administration & dosage*
  • Brain Ischemia* / etiology
  • Brain Ischemia* / pathology
  • Brain Ischemia* / prevention & control
  • Bromodeoxyuridine / metabolism
  • Carotid Artery Diseases / complications
  • Cell Differentiation / drug effects
  • Dibenzothiazepines / administration & dosage*
  • Disease Models, Animal
  • Gene Expression Regulation / drug effects
  • Glial Fibrillary Acidic Protein / metabolism
  • Hippocampus / drug effects
  • Hippocampus / pathology*
  • Male
  • Mice
  • Myelin Basic Protein / metabolism
  • Myelin Sheath / metabolism*
  • Oligodendroglia / drug effects*
  • Proteoglycans / metabolism
  • Quetiapine Fumarate
  • Time Factors

Substances

  • Antigens
  • Antipsychotic Agents
  • Dibenzothiazepines
  • Glial Fibrillary Acidic Protein
  • Myelin Basic Protein
  • Proteoglycans
  • chondroitin sulfate proteoglycan 4
  • Quetiapine Fumarate
  • Bromodeoxyuridine