Dorsomedial Hypothalamic Pathways and Energy Balance

描述(由申请人提供)：下丘脑在维持能量平衡方面起着核心作用。从早期的电刺激或损伤研究到现代的神经回路分析，下丘脑的各种核团，包括弓状核(ARC)、下丘脑腹内侧核(VMH)、室旁核(PVN)和下丘脑外侧区(LH)，在控制食物摄入量和能量平衡方面所起的作用已得到很好的证明。相比之下，下丘脑背内侧核(DMH)在调节摄食和体重方面的作用还不完全清楚。尽管DMH损伤已经被证明影响食物摄入量、体重和线性生长，但这些损伤效应背后的神经电路或这个核对整体能量平衡的基本贡献才刚刚开始解体。最近的一些发现表明，DMH含有多种与摄食相关的神经肽和多肽受体，但这些系统之间可能有助于摄食控制的潜在相互作用尚未确定。 拟议的实验将集中在瘦素、神经肽Y(NPY)、黑素皮质素、促肾上腺皮质激素释放因子(CRF)和胆囊收缩素(CCK)系统，并评估它们在DMH内在能量平衡中可能的相互作用。为了为这些多肽系统之间的潜在相互作用提供基础，我将使用双标记原位杂交组织化学或免疫组织化学或两者的组合来表征DMH神经元及其组织化学关系。在这一神经解剖学特征之后，我将评估DMH基因在改变能量需求的一些治疗中的表达模式，以确定这些DMH多肽系统在能量控制中的功能意义。总之，这些神经化学和功能演示将提供一个关于DMH在能量平衡中的作用的清晰视图

DESCRIPTION (provided by applicant): The hypothalamus plays a central role in maintaining energy homeostasis. From early electrical stimulation or lesion studies to modern neuronal circuitry analyses, roles for various hypothalamic nuclei, including the arcuate nucleus (ARC), ventralmedial hypothalamus (VMH), paraventricular nucleus (PVN) and the lateral hypothalamic area (LH), in the control of food intake and energy balance are well documented. In contrast, the actions of the dorsomedial hypothalamic nucleus (DMH) in regulating feeding and body weight are incompletely understood. Although DMH lesions have been demonstrated to affect food intake, body weight and linear growth, the neural circuitry underlying these lesion effects or the basic contributions of this nucleus to overall energy homeostasis are only beginning to be unraveled. A number of recent findings suggest that the DMH contains multiple feeding related neuropeptides and peptide receptors but the potential interactions among these systems that could contribute to feeding control have not been identified. The proposed experiments will focus on leptin, Neuropeptide Y (NPY), melanocortin, corticotropin-releasing factor (CRF) and cholecystokinin (CCK) systems, and assess their possible interactions within the DMH in energy balance. To provide a basis for potential interactions among these peptide systems, I will use double labeled in situ hybridization histochemistry or immunohistochemistry or combinations of both to characterize DMH neurons and their histochemical relationships. After this neuroanatomical characterization, I will assess patterns of DMH gene expression in response to a number of treatments that alter energy demands to identify the functional significance of these DMH peptide systems in energy control. Together, these neurochemical and functional demonstrations will provide a clear view of the role of the DMH in energy balance