Acute systemic endotoxin administration elevates neuroimmune markers and sickness behaviors in male and female Peromyscus californicus

The California mouse is a biparental monogamous rodent species used to study the neuroendocrine mechanisms underlying social stressors, but there is limited research investigating the neuroimmune response within the species to facilitate our understanding of stress and neuroinflammation interactions. The data herein provide an assessment of behavior, somatic metrics, and gene expression changes within the prefrontal cortex (PFC) and hippocampus (HPC) at 4- and 24-h following a single peripheral injection of the endotoxin lipopolysaccharide (LPS) in males and females. We observed effects of LPS on spleen weights and both males and females demonstrated sickness-like behaviors at 24 h as indicated by assessment of nest building quality. Within both sexes in both the PFC and HPC, proinflammatory genes (i.e., tumor necrosis factor (TNF) and interleukin-1β (IL-1β)) were increased at 4 h following LPS, with a return towards expression levels of saline controls by 24 h. Gene expression of GFAP, Cd68, and Complement C3 were elevated by LPS in both sexes and both brain regions with highest expression observed at 24 h. Given that mitochondria function is impacted by inflammatory mediators, we isolated functional synaptic mitochondria to assess for changes in oxygen consumption. Mitochondria spare capacity was elevated in the PFC 4 h after LPS, but only in males. LPS did not alter mitochondrial function at any time point within the HPC for either sex. Collectively, these data demonstrate that both male and female California mice exhibit peripheral and neuroinflammatory consequences of an acute LPS challenge with relative sparing of synaptic mitochondrial function. These data provide a framework for building California mouse studies focused on the intersection of social stress and inflammation on behavioral outcomes.