The role of peptide mediators and peripheral neural afferents in the development of fever, sickness behavior and in the adaptation to fasting: age-related alterations
The anorexia, somnolence, apathy, allodynia frequently associated with fever, form a syndrome that is called sickness behavior (SB). The SB syndrome that is regarded as a defence mechanism of the infected host, also presents a significant population-wide health-related problem, especially in older populations. In these age-groups the efficacy of the SB in the defence against infections is diminished, the capacity to develop fever is reduced, while anorexia becomes exaggerated, further aggravating age-related loss of body weight (cachexia) leading to sarcopenia (a 20-40% loss of skeletal muscle mass). Peripheral (e.g. capsaicin-sensitive neural afferents) and central regulatory mechanisms (e.g. central neuropeptide systems) contribute to the development of various members of SB that involve the collaboration of several organ systems. These regulatory systems show characteristic age-related alterations. The aim of the program is to uncover age-related alterations in the pyrogenic and anorexigenic mechanisms of SB. We aim to clarify the role of peripheral neural afferents [capsicin-sensitive neural afferents, transient receptor potential vanilloid 1 (TRPV1 receptors)] and that of peptide mediators (e.g. corticotropin-releasing factor, cholecystokinin, somatostatin) in endotoxin- or inflammatory cytokine-induced SB and in the adaptation to fasting. These mechanisms and their age-related alterations will be investigated in different age-groups of Wistar rats and those of knock-out (KO) mouse strains (TRPV1KO, somatostatine type 4 receptor KO, etc.). In order to analyze the above mentioned mechanisms, oxygen consumption, thermoregulatory responses (core and tail skin temperatures) will be recorded. Additionally, circadian rhythm of core temperature, heart rate and spontaneous locomotor activity will be registered in a biotemeletric (MiniMitter) system.
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