Neuroinflammaging underlies emotional disturbances and circadian rhythm disruption in young male senescence-accelerated mouse prone 8 mice

Aging causes psychological dysfunction and neurodegeneration, and can lead to cognitive impairments. Although numerous studies have reported that neurodegeneration and subsequent cognitive impairments are involved in neuroinflammation, relationship between psychological disturbance and neuroinflammation with aging (neuroinflammaging) remains unclear. Here, to clarify the relationship, we examined whether neuroinflammaging affects emotional behaviors in senescence-accelerated mouse prone 8 (SAMP8) mice. Microglial inflammatory responses to a subsequent lipopolysaccharide (LPS) challenge were significantly enhanced in male SAMP8 mice relative to normal aging senescence-accelerated mouse resistant 1 (SAMR1) mice at 17 weeks, but not 8 weeks of age. LPS injection also significantly increased brain and systemic inflammation in SAMP8 mice at 17 weeks. In a battery of behavioral tests, SAMP8 mice at 17 weeks, but not 8 weeks, exhibited anxiety- and depression-like behaviors and circadian rhythm disruption. Taken together, SAMP8 mice at 17 weeks possess a brain microenvironment in which it is easier to trigger neuroinflammatory priming; this may lead to an emergence of anxiety- and depression-like behaviors and circadian rhythm disruption. These findings provide new insights into the temporal relationship between neuroinflammaging and emotion. •SAMP8 mice aged 17 weeks, but not 8 weeks, exhibit a neuroinflammatory priming.•LPS injection enhances neuroinflammatory responses in SAMP8 mice aged 17 weeks.•Emotional disturbances emerge in SAMP8 mice aged 17 weeks.•SAMP8 mice show circadian rhythm disruptions with aging.•The neuroinflammatory priming underlies age-related emotional disturbances.