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

Masashi Kakae1, Jun Miyanohara1, Misa Morishima1

  • 1Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan.

Neuroscience
|April 19, 2019
PubMed

Insights

Transient receptor potential melastatin 2 (TRPM2) channels worsen brain inflammation and cognitive decline in aging mice. Deleting TRPM2 protected against age-related memory loss and brain damage, highlighting its role in aging.

Area of Science:

  • Neuroscience
  • Immunology
  • Aging Research

Background:

  • Aging is associated with cognitive decline and increased brain inflammation.
  • Transient receptor potential melastatin 2 (TRPM2) channels, abundant in immune cells, can worsen inflammatory responses.
  • The role of TRPM2 in age-related brain inflammation and cognitive dysfunction is not fully understood.

Purpose of the Study:

  • To investigate the physiological and pathophysiological role of TRPM2 in age-associated inflammatory responses and cognitive dysfunction.
  • To examine the effects of TRPM2 deletion on cognitive function and brain pathology in young and aged mice.

Main Methods:

  • Comparison of wild-type (WT) and TRPM2 knockout (TRPM2-KO) mice across different age groups (young, middle-aged, and aged).
  • Assessment of cognitive function, including working, cognitive, and spatial memory.
  • Evaluation of brain pathology, including white matter injury, hippocampal damage, microglial activation (Iba1-positive cells), and pro-inflammatory cytokine levels.

Main Results:

  • Middle-aged WT mice showed working and cognitive memory deficits, while aged WT mice exhibited impaired spatial memory.
  • TRPM2-KO mice did not display these age-related cognitive impairments.
  • Aged WT mice presented with white matter injury, hippocampal damage, increased microglial activation, and elevated pro-inflammatory cytokines, which were absent in TRPM2-KO mice.

Conclusions:

  • TRPM2 channels play a critical role in exacerbating inflammatory responses during aging.
  • TRPM2 deletion ameliorates age-associated cognitive dysfunction and brain pathology.
  • Targeting TRPM2 may offer a therapeutic strategy for age-related cognitive decline and neuroinflammation.
Keywords:
TRPM2agingcognitive impairmentcytokinesmicrogliawhite matter injury

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