Abstract：
Lowered glucose availability, sensed by the hindbrain, has been suggested to enhance gluconeogenesis and food intake as well as suppress reproductive function. In fact, our previous histological and in vitro studies suggest that hindbrain ependymal cells function as a glucose sensor. The present study aimed to clarify the hindbrain glucose sensor-hypothalamic neural pathway activated in response to hindbrain glucoprivation to mediate counterregulatory physiological responses. Administration of 2-deoxy-D-glucose (2DG), an inhibitor of glucose utilization, into the fourth ventricle (4V) of male rats for 0.5 hour induced messenger RNA (mRNA) expression of c-fos, a marker for cellular activation, in ependymal cells in the 4V, but not in the lateral ventricle, the third ventricle or the central canal without a significant change in blood glucose and testosterone levels. Administration of 2DG into the 4V for 1 hour significantly increased blood glucose levels, food intake, and decreased blood testosterone levels. Simultaneously, the expression of c-Fos protein was detected in the 4V ependymal cells; dopamine β-hydroxylase-immunoreactive cells in the C1, C2, and A6 regions; neuropeptide Y (NPY) mRNA-positive cells in the C2; corticotropin-releasing hormone (CRH) mRNA-positive cells in the hypothalamic paraventricular nucleus (PVN); and NPY mRNA-positive cells in the arcuate nucleus (ARC). Taken together, these results suggest that lowered glucose availability, sensed by 4V ependymal cells, activates hindbrain catecholaminergic and/or NPY neurons followed by CRH neurons in the PVN and NPY neurons in the ARC, thereby leading to counterregulatory responses, such as an enhancement of gluconeogenesis, increased food intake, and suppression of sex steroid secretion.
摘要：
降低葡萄糖的可用性，后脑感觉到的，有人建议增强糖异生和食物摄入以及抑制生殖功能。事实上,我们以前的组织学和体外研究表明，后脑室管膜细胞作为葡萄糖传感器。本研究旨在阐明后脑葡萄糖传感器-下丘脑神经通路响应后脑葡萄糖代谢而激活，以介导反调节生理反应。2-脱氧-D-葡萄糖（2DG）的给药，葡萄糖利用的抑制剂，入第四脑室(4V)雄性大鼠0.5小时诱导c-fosmRNA表达,细胞激活的标记，在4V的室管膜细胞中，但不是在侧脑室,第三脑室或中央管，血糖和睾酮水平无明显变化。给药2DG进入4V1小时显著增加血糖水平，食物摄入量,和降低血液中的睾丸激素水平。同时,在4V室管膜细胞中检测到c-Fos蛋白的表达；在C1，C2和A6区中检测到多巴胺β-羟化酶免疫反应性细胞；在C2中检测到神经肽Y（NPY）mRNA阳性细胞；下丘脑室旁核（PVN）中的促肾上腺皮质激素释放激素（CRH）mRNA阳性细胞；和弓状核（ARC）中的NPY阳性细胞。一起来看,这些结果表明，降低葡萄糖的可用性，由4V室管膜细胞感知，激活后脑儿茶酚胺能和/或NPY神经元，然后激活PVN中的CRH神经元和ARC中的NPY神经元，从而导致反监管反应，例如糖异生的增强，增加食物摄入量，和抑制性类固醇分泌。
