Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
PLoS One. 2011 May 11;6(5):e19745. doi: 10.1371/journal.pone.0019745.
Some pathological conditions with feeding pattern alterations, including obesity and Huntington disease (HD) are associated with hypothalamic dysfunction and neuronal cell death. Additionally, the hypothalamus is a neurogenic region with the constitutive capacity to generate new cells of neuronal lineage, in adult rodents. The aim of the present work was to evaluate the expression of feeding-related neuropeptides in hypothalamic progenitor cells and their capacity to differentiate to functional neurons which have been described to be affected by hypothalamic dysfunction. Our study shows that hypothalamic progenitor cells from rat embryos grow as floating neurospheres and express the feeding-related neuropeptides Neuropeptide Y (NPY), Agouti-related Protein (AGRP), Pro-OpioMelanocortin (POMC), Cocaine-and-Amphetamine Responsive Transcript (CART) and Orexin-A/Hypocretin-1. Moreover the relative mRNA expression of NPY and POMC increases during the expansion of hypothalamic neurospheres in proliferative conditions.Mature neurons were obtained from the differentiation of hypothalamic progenitor cells including NPY, AGRP, POMC, CART and Orexin-A positive neurons. Furthermore the relative mRNA expression of NPY, CART and Orexin-A increases after the differentiation of hypothalamic neurospheres. Similarly to the adult hypothalamic neurons the neurospheres-derived neurons express the glutamate transporter EAAT3. The orexigenic and anorexigenic phenotype of these neurons was identified by functional response to ghrelin and leptin hormones, respectively. This work demonstrates the presence of appetite-related neuropeptides in hypothalamic progenitor cells and neurons obtained from the differentiation of hypothalamic neurospheres, including the neuronal phenotypes that have been described by others as being affected by hypothalamic neurodegeneration. These in vitro models can be used to study hypothalamic progenitor cells aiming a therapeutic intervention to mitigate feeding dysfunction that are associated with hypothalamic neurodegeneration.
一些伴有摄食模式改变的病理状况，包括肥胖和亨廷顿病（HD），与下丘脑功能障碍和神经元细胞死亡有关。此外，下丘脑是一个具有产生新的神经元谱系细胞的固有能力的神经发生区域，在成年啮齿动物中也是如此。本研究旨在评估下丘脑祖细胞中与摄食相关的神经肽的表达及其分化为功能性神经元的能力，已知这些神经元受到下丘脑功能障碍的影响。我们的研究表明，来自大鼠胚胎的下丘脑祖细胞作为漂浮的神经球生长，并表达与摄食相关的神经肽神经肽 Y（NPY）、肥胖相关蛋白（AGRP）、前阿片黑素细胞皮质素（POMC）、可卡因和安非他命反应转录物（CART）和食欲素-A/下丘脑肽-1。此外，在增殖条件下，下丘脑神经球扩增过程中 NPY 和 POMC 的相对 mRNA 表达增加。成熟神经元是从小鼠下丘脑祖细胞分化而来的，包括 NPY、AGRP、POMC、CART 和食欲素-A 阳性神经元。此外，在分化下丘脑神经球后，NPY、CART 和食欲素-A 的相对 mRNA 表达增加。与成年下丘脑神经元类似，神经球衍生的神经元表达谷氨酸转运蛋白 EAAT3。这些神经元的食欲增强和厌食表型通过对 ghrelin 和瘦素激素的功能反应来鉴定。这项工作证明了在从小鼠下丘脑神经球分化而来的下丘脑祖细胞和神经元中存在与摄食相关的神经肽，包括其他研究人员描述的受下丘脑神经退行性变影响的神经元表型。这些体外模型可用于研究下丘脑祖细胞，旨在进行治疗干预以减轻与下丘脑神经退行性变相关的摄食功能障碍。
