Fatigue is best defined as difficulty in initiating or sustaining voluntary activities, and is thought to be accompanied by deterioration of performance. Fatigue can be caused by many factors such as physical and mental stress, disturbance in the circadian rhythm, and various diseases. For example, following the flu or other types of infections, everyone has experienced a sense of fatigue that can last for days or weeks. The fatigue sensation is thought to be one of the signals for the body to suppress physical activity in order to regain health. The mechanism of induction of the fatigue sensation following viral infection has not been well understood. Although fatigue was once thought to be caused by fever, our recent study with an animal model of viral infection demonstrated that the fatigue sensation is caused not by fever, but rather, by neuroinflammation of brain tissue (Yamato et al., 2014). A positron emission tomography (PET) study in patients with chronic fatigue syndrome/myalgic encephalomyelitis revealed that activation of microglia is involved in neuroinflammation in the brain, and indicated that the intensity of the PET signals evaluating the presence of neuroinflammation was associated with the severity of neuropsychological symptoms (Nakatomi et al., 2014). Other studies have indicated that neuroinflammation is an important precipitating event in chronic neurological disorders including Alzheimer's disease, Parkinson's disease, and depression (Song and Wang, 2011; Fan et al., 2014). Therefore, an understanding of the regulatory mechanisms of neuroinflammation and the prevention of entering the chronic state is important.
