| Animals inhabiting nontropical and boreal latitudes have evolved temporal strategies to coordinate energetically expensive activities such as mating, migration, molt, and care of offspring, at different times of the year. Winter is often a time of energetic crisis for nontropical rodents; energy availability during winter is typically reduced, while the energetic requirements for thermogenesis are high. Small animals have evolved to cope with the “energetic bottleneck” of winter by reducing energetically-demanding activities that are not essential for immediate survival. For example, reproductive activities, growth, and locomotor activity are often curtailed during energy shortages; during the winter, energy is allocated to thermoregulation, cellular maintenance, and in a number of species, to enhance immune function. In other species, however, it appears that energy is not allocated to immune function, and immunity is suppressed in laboratory simulations of winter. The present dissertation experiments were designed to examine the neuroendocrine mechanisms underlying seasonal changes in immunity and energy balance.; The first set of experiments was designed to investigate the role of melatonin in mediating seasonal changes in immune function. Studies using in vitro and pharmacological techniques in combination with genetically altered mice, suggest that melatonin acts directly on immune tissues to enhance immunity. The second set of studies examined how the sympathoadrenal system mediates seasonal changes in immune function. The results of these in vitro and in vivo studies suggest that direct innervation of the spleen and adrenal medullary catecholamines differentially affect photoperiodic changes in immune function, with adrenal medullary catecholamines playing a greater role in long-days, and direct sympathetic nervous system (SNS) innervation of the spleen more involved in mediating immunity in short-days. The third set of experiments tested the role of energetics in immune function, specifically by examining the contribution of leptin, and by manipulating energy availability on the “input” end of the energy balance equation. It appears that leptin acts differentially based on photoperiod, and that leptin indirectly affects immune function in short days by affecting energy balance. In addition, energetically costly activities such as pregnancy, lactation, and 2-DG-induced torpor alter immune function in seasonally-breeding animals.; Taken together, the experiments from this dissertation provide insight into the neuroendocrine mechanisms that mediate seasonal changes in immune function both in species that enhance or inhibit immune function during short, “winter-like” days. Both neural and endocrine factors contribute to the alterations in immune function observed on a seasonal basis. The present studies also provide further evidence that immune function is energetically costly by demonstrating that one of the primary hormonal mediators of energy balance plays a role in altering immune function based on the energy status of an individual. |
