Neurotrophic effects of amylin during development of brainstem projections involved in energy homeostasis

[摘要] The pancreatic hormone amylin inhibits food intake activating neurons in the area postrema (AP) of the brainstem. This excitation is transmitted via neuronal projections to the nucleus of the solitary tract (NTS). Amylin also acts as growth factor in bone cells, pancreatic islets and the kidney. The current study explored whether amylin exerts neurotrophic effects during early brain development that may contribute to the growth of neuronal pathways originating in the AP. The lipophilic tracer DiI was used to analyze AP-NTS projections in postnatal amylin deficient (IAPP-/-) mice and their wildtype littermates (IAPP+/+). In 10 day old neonates the average fiber density in the NTS of IAPP-/-mice was significantly reduced compared to IAPP+/+ littermates. Interestingly, there seemed to be neuronal remodelling processes between postnatal day 10 and 14 which were reflected by a decrease in the NTS fiber density of IAPP+/+. From postnatal day 6 to 9 plasma amylin levels in neonates were similar to amylin levels of adult mice. This study provides first evidence for a critical function of amylin as a neurotrophic factor affecting the development of important brainstem pathways controlling food intake. The present findings substantiate the concept that the developing brain is imprinted by hormonal influences during the perinatal stage. Such processes may have an impact on the risk to develop metabolic diseases (e.g. diabetes mellitus) and excessive body weight (obesity) later in life.

[发布机构] University of Zurich

[效力级别] 570 Life sciences

[关键词] Institute of Veterinary Physiology;570 Life sciences;biology