Abstract
Triggering receptor expressed on myeloid cells 2 (TREM2), a receptor exclusively expressed by microglia in the brain, modulates microglial immune homeostasis. Human genetic studies have shown that the loss-of-function mutations in TREM2 signaling are strongly associated with an elevated risk of age-related neurodegenerative diseases including Alzheimer's disease (AD). Numerous studies have investigated the impact of TREM2 deficiency in the pathogenic process of AD. However, the role of TREM2 in shaping neuronal and cognitive function during normal aging is underexplored. In the present study, we employed behavioral, electrophysiological, and biochemical approaches to assess cognitive and synaptic function in male and female young and aged TREM2-deficient (Trem22/2) mice compared with age-matched, sex-matched, and genetic background-matched wild-type (WT) C57BL/6J controls. Young Trem22/2 mice exhibited normal cognitive function and synaptic plasticity but had increased dendritic spine density compared with young WT. Unexpectedly, aged Trem22/2 mice showed superior cognitive performance compared with aged WT controls. Consistent with the behavioral data, aged Trem22/2 mice displayed significantly enhanced hippocampal long-term potentiation (LTP) and increased dendritic spine density and synaptic markers compared with aged WT mice. Taken together, these findings suggest that loss of TREM2 affects the neuronal structure and confers resilience to age-related synaptic and cognitive impairment during non-pathogenic aging.
Original language | English (US) |
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Pages (from-to) | 9552-9563 |
Number of pages | 12 |
Journal | Journal of Neuroscience |
Volume | 40 |
Issue number | 50 |
DOIs | |
State | Published - Dec 9 2020 |
Bibliographical note
Publisher Copyright:© 2020 the authors
Keywords
- Aging
- Dendritic spine density
- Learning and memory
- Long-term potentiation
- Synaptic plasticity
- TREM2
PubMed: MeSH publication types
- Journal Article
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't