Mechanism of cognitive impairment and white matter damage in the MK-801 mice model of schizophrenia treated with quetiapine

Behav Brain Res. 2024 Mar 12:461:114838. doi: 10.1016/j.bbr.2023.114838. Epub 2023 Dec 28.

Abstract

Schizophrenia has been linked to cognitive impairment and white matter damage in a growing number of studies this year. In this study, we used the MK-801-induced schizophrenia-like mice model to investigate the effects of quetiapine on behavioral changes and myelin loss in the model mice. The subjects selected for this study were C57B6/J male mice, MK-801 (1 mg/kg/d intraperitoneal injection) modeling for 1 week and quetiapine (10 mg/kg/d intraperitoneal injection) treatment for 2 weeks. Behavioral tests were then performed using the three-chamber paradigm test and the Y maze test. Moreover, western blot, immunohistochemistry, and immunofluorescence were conducted to investigate the changes in oligodendrocyte spectrum markers. In addition, we performed some mechanism-related proteins by western blot. Quetiapine ameliorated cognitive impairment and cerebral white matter damage in MK-801 model mice, and the mechanism may be related to the PI3K/AKT pathways. The present study suggests that quetiapine has a possible mechanism for treating cognitive impairment and white matter damage caused by schizophrenia.

Keywords: Cognitive impairment; MK-801; Myelin; Oligodendrocyte; Quetiapine; Schizophrenia; White matter.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cognitive Dysfunction* / drug therapy
  • Dizocilpine Maleate / adverse effects
  • Humans
  • Male
  • Mice
  • Phosphatidylinositol 3-Kinases / metabolism
  • Quetiapine Fumarate / pharmacology
  • Schizophrenia* / chemically induced
  • Schizophrenia* / drug therapy
  • Schizophrenia* / metabolism
  • White Matter* / metabolism

Substances

  • Quetiapine Fumarate
  • Dizocilpine Maleate
  • Phosphatidylinositol 3-Kinases