Pathophysiological Role of TRPM2 in Age-Related Cognitive Impairment in Mice

• Kakae, Masashi

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

• Miyanohara, Jun

  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

• Mori, Yasuo

  Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, 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

Aging causes various functional changes, including cognitive impairment and inflammatory responses in the brain. Transient receptor potential melastatin 2 (TRPM2), a Ca2+-permeable channel expressed abundantly in immune cells, exacerbates inflammatory responses. Previously, we reported that TRPM2 on resident microglia plays a critical role in exacerbating inflammation, white matter injury, and cognitive impairment during chronic cerebral hypoperfusion; however, the physiological or pathophysiological role of TRPM2 during age-associated inflammatory responses remains unclear. Therefore, we examined the effects of TRPM2 deletion in young (2–3 months) and older (12–24 months) mice. Compared with young wild-type (WT) mice, middle-aged (12–16 months) WT mice showed working and cognitive memory dysfunction and aged (20–24 months) WT mice exhibited impaired spatial memory. However, these characteristics were not seen in TRPM2 knockout (TRPM2-KO) mice. Consistent with the finding of cognitive impairment, aged WT mice exhibited white matter injury and hippocampal damage and an increase in the number of Iba1-positive cells and amounts of pro-inflammatory cytokines in the brain; these characteristics were not seen in TRPM2-KO mice. These findings suggest that TRPM2 plays a critical role in exacerbating inflammatory responses and cognitive dysfunction during aging.

Journal

• Neuroscience

  Neuroscience 408 204-213, 2019-06-01

  Elsevier Ltd

Keywords

• aging
• cognitive impairment
• white matter injury
• TRPM2
• microglia
• cytokines

Details

• CRID: 1050001338306723584
• NII Article ID: 120006630990
• ISSN: 03064522
• ISSN: 18737544
• DOI: 10.1016/j.neuroscience.2019.04.012
• HANDLE: 2433/241618
• Web Site: https://api.elsevier.com/content/article/PII:S0306452219302520?httpAccept=text/xml
• Web Site: https://api.elsevier.com/content/article/PII:S0306452219302520?httpAccept=text/plain
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • Crossref
  • CiNii Articles
  • KAKEN