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Title: Pathophysiological Role of TRPM2 in Age-Related Cognitive Impairment in Mice
Authors: Kakae, Masashi
Miyanohara, Jun
Morishima, Misa
Nagayasu, Kazuki
Mori, Yasuo
Shirakawa, Hisashi
Kaneko, Shuji
Author's alias: 森嶋, 美沙
永安, 一樹
森, 泰生
白川, 久志
金子, 周司
Keywords: aging
cognitive impairment
white matter injury
TRPM2
microglia
cytokines
Issue Date: 1-Jun-2019
Publisher: Elsevier Ltd
Journal title: Neuroscience
Volume: 408
Start page: 204
End page: 213
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.
Rights: © 2019. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/.
The full-text file will be made open to the public on 1 June 2020 in accordance with publisher's 'Terms and Conditions for Self-Archiving'.
This is not the published version. Please cite only the published version. この論文は出版社版でありません。引用の際には出版社版をご確認ご利用ください。
URI: http://hdl.handle.net/2433/241618
DOI(Published Version): 10.1016/j.neuroscience.2019.04.012
PubMed ID: 30999030
Appears in Collections:Journal Articles

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