Behavioral change in response to low-grade non-infectious stimuli: Findings and potential neuroimmune mechanisms.

摘要

Individuals afflicted with a pathogenic infection exhibit symptoms including lethargy, malaise, listlessness, loss of interest in social and environmental surroundings, and anorexia. Together, these symptoms comprise what is recognized as "sickness behavior." Sickness behavior represents a conserved, motivational behavioral state that, with the induction of fever, serves to help an organism combat infection and ultimately survive. Long dismissed as an unavoidable consequence of the physiological changes resulting from pathogen-dependent immune activation, it is now well known that sickness behavior is a consequence of neuroimmune activation. Neuroimmunity serves as a bridge between the peripheral immune system and the central nervous system, acting to signal bi-directionally both centrally and humorally between these two systems. Proinflammatory cytokines, most often originating from innate immune cells, are the principle signaling molecules from the periphery to the brain. Sickness behavior is typically transient, resolving upon pathogen clearance. Exacerbated or unchecked proinflammation, such as occurs in chronic disease or autoimmune disorders, leads to maladaptive behaviors such as depression and anxiety. Neuroimmune activation often also causes cognitive impairments in addition to sickness, depressive or anxietal behaviors. It is widely recognized that non-infectious stimuli, such as ionizing radiation or hypoxia can activate the neuroimmune system and cause sickness behavior and other behaviors. This literature review focuses on the different ways activation of the neuroimmune system can occur, the inflammatory and behavioral consequences of its activation and some of the modulators of neuroimmune communication. Chapters 2 and 3 will provide evidence showing low dose ionizing radiation and chronic low-grade hypoxia can result in the display of typical neuroimmune-mediated behaviors, as well as other physiological changes. Taken together, these findings show that behavioral change can be induced by lower doses of ionizing radiation and hypoxia than have previously been reported, and that neuroimmune signaling can occur where and when it was previously unknown to.