TY - JOUR
T1 - Loss of TREM2 confers resilience to synaptic and cognitive impairment in aged mice
AU - Qu, Wenhui
AU - Li, Ling
N1 - Publisher Copyright:
© 2020 the authors
PY - 2020/12/9
Y1 - 2020/12/9
N2 - 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.
AB - 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.
KW - Aging
KW - Dendritic spine density
KW - Learning and memory
KW - Long-term potentiation
KW - Synaptic plasticity
KW - TREM2
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U2 - 10.1523/JNEUROSCI.2193-20.2020
DO - 10.1523/JNEUROSCI.2193-20.2020
M3 - Article
C2 - 33139402
AN - SCOPUS:85097967793
SN - 0270-6474
VL - 40
SP - 9552
EP - 9563
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 50
ER -