cytokine expression and other brain injury-associated biomarkers have been observed in infected versus uninfected outbred and inbred mice. Preliminary data have also suggested a possible link between significant memory impairment and cytokine production associated with T. canis infection. Mice provide a useful, replicable animal model with significant applicability and ease of manipulation. Understanding the cerebral host–parasite relationship may shed some light on the cryptic symptoms of human infection where patients often present with other CNS disorders such as epilepsy and mental retardation.
Immune–neural connections: how the immune system’s response to infectious agents influences behavior
Humans and animals use the classical five senses of sight, sound, touch, smell and taste to monitor their environment. The very survival of feral animals depends on these sensory perception systems, which is a central theme in scholarly research on comparative aspects of anatomy and physiology. But how do all of us sense and respond to an infection? We cannot see, hear, feel, smell or taste bacterial and viral pathogens, but humans and animals alike are fully aware of symptoms of sickness that are caused by these microbes. Pain, fatigue, altered sleep pattern, anorexia and fever are common symptoms in both sick animals and humans. Many of these physiological changes represent adaptive responses that are considered to promote animal survival, and this constellation of events results in sickness behavior. Infectious agents display a variety of pathogen-associated molecular patterns (PAMPs) that are recognized by pattern recognition receptors (PRRs). These PRR are expressed on both the surface [e.g. Toll-like receptor (TLR)-4] and in the cytoplasm [e.g. nucleotide-binding oligomerization domain (Nod)-like receptors] of cells of the innate immune system, primarily macrophages and dendritic cells. These cells initiate and propagate an inflammatory response by stimulating the synthesis and release of a variety of cytokines. Once an infection has occurred in the periphery, both cytokines and bacterial toxins deliver this information to the brain using both humoral and neuronal routes of communication. For example, binding of PRR can lead to activation of the afferent vagus nerve, which communicates neuronal signals via the lower brain stem (nucleus tractus solitarius) to higher brain centers such as the hypothalamus and amygdala. Blood-borne cytokines initiate a cytokine response from vascular endothelial cells that form the blood–brain barrier (BBB). Cytokines can also reach the brain directly by leakage through the BBB via circumventricular organs or by being synthesized within the brain, thus forming a mirror image of the cytokine milieu in the periphery. Although all cells within the brain are capable of initiating cytokine secretion, microglia have an early response to incoming neuronal and humoral stimuli. Inhibition of proinflammatory cytokines that are induced following bacterial infection blocks the appearance of sickness behaviors. Collectively, these data are consistent with the notion that the immune system communicates with the brain to regulate behavior in a way that is consistent with animal survival.
Toxoplasma gondii infection, from predation to schizophrenia: can animal behaviour help us understand human behaviour?NEW APPROACHES
We examine the role of the protozoan Toxoplasma gondii as a manipulatory parasite and question what role study of infections in its natural intermediate rodent hosts and other secondary hosts, including humans, may elucidate in terms of the epidemiology, evolution and clinical applications of infection. In particular, we focus on the potential association between T. gondii and schizophrenia. We introduce the novel term ‘T. gondii–rat manipulation–schizophrenia model’ and propose how future behavioural research on this model should be performed from a biological, clinical and ethically appropriate perspective.
Toxoplasma gondii infection and behaviour – location, location, location?
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