Descending raphe circuits for adaptive thermogenesis

用于自适应产热的下降中缝电路

• 批准号: 505389599
• 负责人: Dr. Henning Fenselau, Ph.D.
• 金额: --
• 依托单位: Institut für Zoologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/505389599?language=en
• 关键词: Descending; raphe; circuits; adaptive; thermogenesis

Adaptive thermogenesis is a vital homeostatic process for body temperature regulation. Because it increases systemic energy expenditure, adaptive thermogenesis represents a significant factor in energy balance. Descending sympathetic pathways, which consist of brain neurocircuits projecting to spinal sympathetic preganglionic neurons, connect the brain to peripheral thermogenic tissues, and thereby critically contribute to the central control of adaptive thermogenesis. Previous histological and pharmacological studies identified the raphe pallidus (rPa) of the brainstem as a key component of these thermogenic pathways. However, the specific rPa neuron population, which sends descending projections to the spinal cord, and their downstream sympathetic neurocircuits controlling adaptive thermogenesis remain to be elucidated. Further, the neuroactive chemicals (i.e., neurotransmitters and neuromodulators) conveying thermogenic signals across synapses between rPa neurons and postsynaptic spinal sympathetic preganglionic neurons remain unclear. The latter is of particular interest because rPa neurons express various potential neurotransmitters and neuromodulators that are known to have a role in regulating energy expenditure and body weight – such as thyrotropin-releasing hormone and serotonin. Therefore, the overarching aims of this comprehensive research proposal are to define the thermoregulatory function of molecularly defined rPa neurons, and to elucidate the physiological function of the neuroactive chemicals they release onto spinal sympathetic preganglionic neurons. These complementary aims will collectively gain greater insights into the integral components of sympathetic pathways in controlling adaptive thermogenesis, and brain control of energy balance and body weight homeostasis.

适应性产热是调节体温的重要动态平衡过程。因为它增加了全身的能量消耗，适应性产热是能量平衡的一个重要因素。下行交感神经通路由投射到脊髓交感节前神经元的脑神经回路组成，将大脑与周围产热组织联系起来，从而对适应性产热的中枢控制起着关键作用。以往的组织学和药理学研究证实，脑干的中缝苍白核(RPA)是这些产热途径的关键组成部分。然而，向脊髓发送下行投射的特定RPA神经元群体及其下游控制适应性产热的交感神经回路仍有待阐明。此外，通过RPA神经元和突触后脊髓交感节前神经元之间的突触传递产热信号的神经活性化学物质(即神经递质和神经调节剂)仍不清楚。后者特别令人感兴趣，因为RPA神经元表达各种潜在的神经递质和神经调节剂，已知这些物质在调节能量消耗和体重方面发挥作用--如促甲状腺激素释放激素和5-羟色胺。因此，这一综合性研究计划的主要目的是确定分子定义的RPA神经元的体温调节功能，并阐明它们向脊髓交感节前神经元释放的神经活性化学物质的生理功能。这些互补的目标将共同获得更多关于交感神经通路在控制适应性产热以及大脑控制能量平衡和体重动态平衡方面的组成部分的更多见解。