| First Author | Kakae M | Year | 2019 |
| Journal | Neuroscience | Volume | 408 |
| Pages | 204-213 | PubMed ID | 30999030 |
| Mgi Jnum | J:282855 | Mgi Id | MGI:6384302 |
| Doi | 10.1016/j.neuroscience.2019.04.012 | Citation | Kakae M, et al. (2019) Pathophysiological Role of TRPM2 in Age-Related Cognitive Impairment in Mice. Neuroscience 408:204-213 |
| abstractText | Aging causes various functional changes, including cognitive impairment and inflammatory responses in the brain. Transient receptor potential melastatin 2 (TRPM2), a Ca(2+)-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 (2-3months) and older (12-24months) mice. Compared with young wild-type (WT) mice, middle-aged (12-16months) WT mice showed working and cognitive memory dysfunction and aged (20-24months) 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. |
