Depletion of microglia ameliorates white matter injury and cognitive impairment in a mouse chronic cerebral hypoperfusion model

• Kakae, Masashi

  Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University

• Tobori, Shota

  Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University

• Morishima, Misa

  Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University

• Nagayasu, Kazuki

  Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University

• Shirakawa, Hisashi

  Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University

• Kaneko, Shuji

  Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University

Abstract

Microglia are immune cells in the central nervous system (CNS) and essential for homeostasis that are important for both neuroprotection and neurotoxicity, and are activated in a variety of CNS diseases. Microglia aggravate cognitive impairment induced by chronic cerebral hypoperfusion, but their precise roles under these conditions remain unknown. Here, we used PLX3397, a colony-stimulating factor 1 receptor inhibitor, to deplete microglia in mice with chronic cerebral hypoperfusion induced by bilateral common carotid artery stenosis (BCAS). Cognitive impairment induced 28 days after BCAS was significantly improved in mice fed a diet containing PLX3397. In PLX3397-fed mice, microglia were depleted and white matter injury induced by BCAS was suppressed. In addition, the expression of proinflammatory cytokines, interleukin 6 and tumor necrosis factor alpha, was suppressed in PLX3397-fed mice. Taken together, these findings suggest that microglia play destructive roles in the development of cognitive impairment and white matter injury induced by chronic cerebral hypoperfusion. Thus, microglia represent a potential therapeutic target for chronic cerebral hypoperfusion-related diseases.

Journal

• Biochemical and Biophysical Research Communications

  Biochemical and Biophysical Research Communications 514 (4), 1040-1044, 2019-07-05

  Elsevier BV

Keywords

• Chronic cerebral hypoperfusion
• Cognitive impairment
• White matter injury
• Microglia
• Cytokines
• Colony-stimulating factor 1

Details

• CRID: 1050001202952764032
• NII Article ID: 120006636645
• NII Book ID: AA00564395
• ISSN: 0006291X
• ISSN: 10902104
• DOI: 10.1016/j.bbrc.2019.05.055
• HANDLE: 2433/241701
• Web Site: https://api.elsevier.com/content/article/PII:S0006291X19309234?httpAccept=text/xml
• Web Site: https://api.elsevier.com/content/article/PII:S0006291X19309234?httpAccept=text/plain
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • Crossref
  • CiNii Articles
  • KAKEN