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首页> 外文期刊>The European Journal of Neuroscience >Whole-brain mapping of amylin-induced neuronal activity in receptor activity-modifying protein 1/3 knockout mice
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Whole-brain mapping of amylin-induced neuronal activity in receptor activity-modifying protein 1/3 knockout mice

机译：受体活性改性蛋白1/3敲除小鼠中淀粉蛋白诱导的神经元活性的全脑映射

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The pancreatic hormone amylin plays a central role in regulating energy homeostasis and glycaemic control by stimulating satiation and reducing food reward, making amylin receptor agonists attractive for the treatment of metabolic diseases. Amylin receptors consist of heterodimerized complexes of the calcitonin receptor and receptor-activity modifying proteins subtype 1-3 (RAMP1-3). Neuronal activation in response to amylin dosing has been well characterized, but only in selected regions expressing high levels of RAMPs. The current study identifies global brain-wide changes in response to amylin and by comparing wild type and RAMP1/3 knockout mice reveals the importance of RAMP1/3 in mediating this response. Amylin dosing resulted in neuronal activation as measured by an increase in c-Fos labelled cells in 20 brain regions, altogether making up the circuitry of neuronal appetite regulation (e.g., area postrema (AP), nucleus of the solitary tract (NTS), parabrachial nucleus (PB), and central amygdala (CEA)). c-Fos response was also detected in distinct nuclei across the brain that typically have not been linked with amylin signalling. In RAMP1/3 knockout amylin induced low-level neuronal activation in seven regions, including the AP, NTS and PB, indicating the existence of RAMP1/3-independent mechanisms of amylin response. Under basal conditions RAMP1/3 knockout mice show reduced neuronal activity in the hippocampal formation as well as reduced hip-pocampal volume, suggesting a role for RAMP1/3 in hippocampal physiology and maintenance. Altogether these data provide a global map of amylin response in the mouse brain and establishes the significance of RAMP1/3 receptors in relaying this response.
机译：胰淀素通过刺激饱腹感和减少食物奖励，在调节能量平衡和血糖控制中起着核心作用，使胰淀素受体激动剂对代谢性疾病的治疗具有吸引力。胰淀素受体由降钙素受体和受体活性修饰蛋白1-3亚型（RAMP1-3）的异二聚复合物组成。胰淀素给药引起的神经元激活已经得到了很好的描述，但仅在表达高水平RAMP的选定区域。目前的研究确定了胰淀素对全脑的反应变化，通过比较野生型和RAMP1/3基因敲除小鼠，揭示了RAMP1/3在介导这种反应中的重要性。通过在20个脑区增加c-Fos标记的细胞来测量，杏仁素剂量导致神经元激活，共同构成神经元食欲调节回路（例如，后区（AP）、孤束核（NTS）、臂旁核（PB）和中央杏仁核（CEA））。c-Fos反应也在大脑中不同的核团中检测到，这些核团通常与胰淀素信号无关。在RAMP1/3基因敲除后，胰淀素在包括AP、NTS和PB在内的七个区域诱导了低水平的神经元激活，这表明存在非RAMP1/3依赖的胰淀素反应机制。在基础条件下，RAMP1/3基因敲除小鼠的海马结构神经元活性降低，髋关节容积减少，表明RAMP1/3在海马生理和维持中起作用。总之，这些数据提供了小鼠大脑中胰淀素反应的全局图，并确定了RAMP1/3受体在传递这种反应中的重要性。

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