Memory deficits in males and females long after subchronic immune challenge

ABSTRACT Memory impairments and cognitive decline persist long after recovery from major illness or injury, and correlate with increased risk of later dementia. Here we developed a subchronic peripheral immune challenge model to examine delayed and persistent memory impairments in females and in males. We show that intermittent injections of either lipopolysaccharide or Poly I:C cause memory decline in both sexes that are evident eight weeks after the immune challenge. Importantly, we observed sex-specific patterns of deficits. Females showed impairments in object recognition one week after challenge that persisted for at least eight weeks. In contrast, males had intact memory one week after the immune challenge but exhibited broad impairments in memory tasks including object recognition, and both context and tone fear conditioning several months later. The differential patterns of memory deficits in males and in females were observed without sustained microglial activation or changes in blood-brain barrier permeability. Together, these data suggest that transient neuroimmune activity results in differential vulnerabilities of females and males to memory decline after immune challenge. This model will be an important tool for determining the mechanisms in both sexes that contribute to memory impairments that develop over the weeks and months after recovery from illness. Future studies using this model will provide new insights into the role of chronic inflammation in the pathogenesis of long-lasting memory decline and dementias.