1. Pathophysiological Role of TRPM2 in Age-Related Cognitive Impairment in Mice.
- Author
-
Kakae M, Miyanohara J, Morishima M, Nagayasu K, Mori Y, Shirakawa H, and Kaneko S
- Subjects
- Aging pathology, Aging psychology, Animals, Calcium-Binding Proteins metabolism, Cognitive Dysfunction genetics, Cognitive Dysfunction pathology, Cytokines metabolism, Hippocampus metabolism, Hippocampus pathology, Inflammation pathology, Mice, Mice, Knockout, Microfilament Proteins metabolism, Microglia metabolism, Recognition, Psychology physiology, TRPM Cation Channels genetics, White Matter metabolism, White Matter pathology, Aging metabolism, Cognitive Dysfunction metabolism, Inflammation metabolism, Microglia pathology, Spatial Memory physiology, TRPM Cation Channels metabolism
- Abstract
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 (2-3 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., (Copyright © 2019 IBRO. Published by Elsevier Ltd. All rights reserved.)- Published
- 2019
- Full Text
- View/download PDF