Microglial proliferation attenuates sickness responses in adult mice during endotoxin-induced inflammation

Abstract

We previously reported that the single peripheral administration of lipopolysaccharide (LPS) induced robust and transient microglial proliferation or increased the microglial population in the circumventricular organs (CVOs) and other regions, including the hypothalamus, medulla oblongata, and limbic system. However, the functional significance of an increased microglial population during endotoxin-induced inflammation remains unclear. The present study showed microglial proliferation in the mouse brain during inflammation induced by 50 mg/kg zymosan, 160 nmol/kg prostaglandin E2, and 5 mg/kg LPS. The inhibition of LPS-induced microglial proliferation with a continuous i.c.v. infusion of mitotic inhibitor cytosine arabinoside (AraC) caused persistent decreases in body weight and food and water intakes. The continuous infusion of AraC also prolonged LPS-induced sickness responses, such as lower locomotor activity and core body temperature. Collectively, the present results indicate that a transient increase in the microglial population is beneficial during endotoxin-induced inflammation in the mouse brain because it attenuates sickness responses.