Triggering receptor expressed on myeloid cells 2 knockdown exacerbates aging-related neuroinflammation and cognitive deficiency in senescence-accelerated mouse prone 8 mice

Abstract

As a major characteristic of aging process, neuroinflammation is involved in the pathogenesis of several aging-related diseases including Alzheimer's disease (AD). Triggering receptor expressed on myeloid cells 2 (TREM2) is a newly identified risk gene for AD, which regulates inflammatory process in peripheral tissues via modulating the release of inflammatory cytokines. However, the role of TREM2 in aging-related neuroinflammation, cognitive deficiency, and AD-like neuropathology is unclear so far. Here, we detected the protein levels of TREM2 in brain of 3-, 7-, and 11-month-old senescence-accelerated mouse prone 8 (SAMP8) mice and observed that TREM2 levels were increased during aging process. We then knocked down TREM2 expression in brain of SAMP8 mice by nonviral RNA interference and found a significant increase in proinflammatory cytokines including tumor necrosis factor-α and interleukin (IL)-6, which was accompanied by a reduction in IL-10. Meanwhile, more obvious neuronal and synaptic losses and cognitive impairment were observed. These findings indicate that TREM2 may play a protective role against aging-related neuroinflammation and cognitive impairment.

Keywords: Aging; Alzheimer's disease; Cognitive deficiency; Neuroinflammation; SAMP8; SAMR1; TREM2.