ENVIRONMENTAL TEMPERATURE, SNS DEVELOPMENT AND OBESITY

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The long-term goal of this project is to determine how environmental exposures during development contribute to acquisition of obese or hypertensive traits in the adult. If successful, it may be possible to devise strategies for early intervention which might prevent or at least forestall the development of these disorders. The studies proposed in this application address the lasting influence of the thermal environment in which neonatal animals are reared on an animal's susceptibility to become obese as an adult. During intrauterine life thermal homeostasis is maintained by maternal mechanisms, while after birth neonatal animals are increasingly self-reliant for defense of body temperature. It is the contention of the applicants that the thermoregulatory demands placed upon the newborn organism and its response to them early in life will affect the regulation of these physiological systems into adulthood. In particular, this investigation focuses upon the impact of early environmental temperature on the development of the sympathetic nervous system (SNS). Studies planned address specifically whether environmental temperature during the first two months of life affects the density of sympathetic innervation in peripheral tissues and/or the central regulation of SNS activity in response to alterations in temperature and diet. Studies will also examine the role of nerve growth factor (NGF) and neurotrophin-3 in mediating the changes in peripheral sympathetic innervation consequent to early thermal exposure. Whether these postulated effects of NGF are due to local production of NGF in the target tissues themselves or to circulating levels of NGF will be determined. The impact of rearing temperature on blood pressure and glucose tolerance in adult animals will also be examined.