Hypothalamic neurosphere progenitor cells in low birth-weight rat newborns: neurotrophic effects of leptin and insulin.
Hypothalamic neurosphere progenitor cells in low birth-weight rat newborns: neurotrophic effects of leptin and insulin.
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DOI：
10.1016/j.brainres.2010.12.080
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发表时间：
2011-03-10
期刊：
影响因子：
2.9
通讯作者：
Ross MG
中科院分区：
文献类型：
--
作者：
Desai M;Li T;Ross MG
低出生体重（LBW）的后代表现出减少下丘脑神经饱腹途径和失调的信号，导致程序性摄食过多和成人肥胖。下丘脑食欲回路在生命早期在神经营养激素（瘦素，胰岛素）的影响下发展。值得注意的是，LBW新生儿的血浆瘦素和胰岛素水平降低。由于神经元和神经胶质细胞来源于神经元祖细胞（NPC），我们推测NPC的程序性损伤可能导致LBW后代下丘脑神经通路发育减少。对照组母鼠自由进食，而研究母鼠从妊娠第10天至第21天（LBW）限制50%的食物。在第1天的年龄，下丘脑NPC培养的神经球（NS）和治疗瘦素/胰岛素。我们分析了体外NPC增殖和分化为神经元/星形胶质细胞，促进增殖的信号分子（激活的Notch 1及其下游靶点Hes 1）的表达和体内NPC增殖和迁移。在基础和刺激条件下，LBW后代的NPC分裂和迁移的体内证据受损，并减少体外增殖和分化为神经元和星形胶质细胞的证据。在基础和刺激条件下，LBW神经球中Notch 1和Hes 1表达减少，表明神经球内祖细胞群减少或细胞密度降低。
Low birth-weight (LBW) offspring exhibit reduced hypothalamic neural satiety pathways and dysregulated signaling leading to programmed hyperphagia and adult obesity. Hypothalamic appetite circuits develop during early life, under the influence of neurotrophic hormones (leptin, insulin). Notably, LBW newborns have reduced plasma leptin and insulin levels. As neurons and glia arise from neuronal progenitor cells (NPC), we postulated that a programmed impairment of NPCs may contribute to reduced hypothalamic neural pathway development in LBW offspring. Control dams received ad libitum food, whereas study dams were 50% food-restricted from pregnancy day 10 to 21 (LBW). At day 1 of age, hypothalamic NPCs were cultured as neurospheres (NS) and treated with leptin/insulin. We analyzed in vitro NPCs proliferation and differentiation into neurons/ astrocytes, expression of signal molecules promoting proliferation (activated Notch1 and its downstream target, Hes1) and in vivo NPC proliferation and migration. LBW offspring had impaired in vivo evidence of NPC division and migration, and reduced in vitro evidence of proliferation and differentiation to neurons and astrocytes, under basal and stimulated conditions. The reduced Notch1 and Hes1 expression in LBW neurosphere, under both basal and stimulated conditions, suggests a reduced progenitor cell population or reduced cell density within the neurosphere.
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