Role of Parabrachial Nucleus Neuropeptides in Feeding

描述（由申请方提供）：进食和代谢障碍，如肥胖、厌食、贪食、发育不良、胃反流、恶病质、早饱、胃排空延迟、味觉障碍和嗅觉丧失，可导致包括高血压、中风、糖尿病和心脏病在内的疾病，并造成许多医疗保健费用。阐明控制进食的神经系统是临床和基础科学的基本目标。研究已经确定了对影响进食和肥胖的激素敏感的大脑区域：瘦素，饥饿素和胰岛素。科学家们已经确定了大脑中对这些激素敏感的神经肽，并作为下游介质影响进食和代谢。这些神经肽，如神经肽Y（NPY）和黑色素浓集激素（MCH），在前脑和后脑位置起作用或具有受体。未来研究的一个重要目标是确定这些神经肽如何在脑干核中起作用，并确定这些核如何与前脑核相互作用（例如，下丘脑）对瘦素、生长素释放肽和胰岛素敏感。该建议将评估MCH和NPY对脑桥臂旁核（PBN）中的进食和电生理味觉和内脏反应的影响，PBN是一种脑干核，其接收显著重叠的味觉和内脏传入输入，接收来自下丘脑的直接NPY和MCH输入，并将输出发送到控制口腔运动的脑干核团。第一个实验评估了直接PBN微量注射MCH和NPY以及各自的拮抗剂对摄食微观结构的影响。以下实验评估当MCH和NPY以及各自的拮抗剂应用于脑室或直接在PBN神经元周围显微注射时，MCH和NPY对神经PBN味觉和胃扩张反应的影响。如果直接PBN应用MCH或NPY影响摄食，则应在神经生理学水平上观察，并有助于更好地阐明下丘脑神经肽在脑干中的功能作用。

DESCRIPTION (provided by applicant): Feeding and metabolic disorders such as obesity, anorexia, bulimia, failure to thrive, gastric reflux, cachexia, early satiety, delayed gastric emptying, dysgeusia, and anosmia contribute to diseases including hypertension, stroke, diabetes, and heart disease, and account for many health-care costs. Elucidating the neural systems that control feeding is a fundamental goal for clinical as well as basic science. Studies have identified brain areas that are sensitive to hormones that affect feeding and adiposity: leptin, ghrelin, and insulin. Scientists have identified neuropeptides in the brain that are sensitive to these hormones and act as downstream mediators to influence feeding and metabolism. These neuropeptides, such as neuropeptide Y (NPY), and melanin-concentrating hormone (MCH), act or have receptors in forebrain and hindbrain locations. An important goal for future research is to determine how such neuropeptides function in brainstem nuclei and to determine how these nuclei interact with forebrain nuclei (e.g., hypothalamus) that are sensitive to leptin, ghrelin, and insulin. This proposal will evaluate the effects of MCH and NPY on feeding and electrophysiological taste and visceral responses in the pontine parabrachial nucleus (PBN), a brainstem nucleus that receives significantly overlapping taste and visceral afferent inputs, receives direct NPY and MCH input from the hypothalamus, and sends output to brainstem nuclei controlling oral movement. The first experiments assess effects of direct PBN microinjectons of MCH and NPY and respective antagonists on feeding microstructure. Following experiments assess the effects of MCH and NPY on neural PBN gustatory and gastric distension responses when MCH and NPY and respective antagonists are applied to brain ventricles or microinjected directly around PBN neurons. If direct PBN application of MCH or NPY affects feeding, this should be observed at the neurophysiological level and will serve to better clarify the functional role(s) of hypothalamic neuropeptides in the brainstem.