Neonatal leptin administration alters regional brain volumes and blocks neonatal growth restriction-induced behavioral and cardiovascular dysfunction in male mice.
Neonatal leptin administration alters regional brain volumes and blocks neonatal growth restriction-induced behavioral and cardiovascular dysfunction in male mice.
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DOI：
10.1203/pdr.0b013e3182110c7d
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发表时间：
2011-05
影响因子：
3.6
通讯作者：
Roghair RD
中科院分区：
文献类型：
--
作者：
Erkonen GE;Hermann GM;Miller RL;Thedens DL;Nopoulos PC;Wemmie JA;Roghair RD
早产常并发新生儿生长受限和神经发育障碍。由于全球营养过剩增加了成人代谢综合征的风险，我们寻求有针对性的干预措施。早产和围产期生长受限降低了循环中神经营养激素瘦素的水平。我们假设补充瘦素可以使早期新生儿生长受限小鼠的结局正常化。将幼仔培育成6或12窝，以引起不同的生长模式。从第4-14天，每窝中的幼仔接受盐水或瘦素注射。在4个月时，小鼠接受尾袖血压测量、行为测试和MRI。在12窝中饲养的小鼠的断奶体重和瘦素水平降低。新生儿瘦素给药使血浆瘦素水平正常化而不影响新生儿生长。瘦素替代还使新生生长受限雄性小鼠中观察到的高血压、压力相关的不动性、条件性恐惧和杏仁核增大正常化。在对照组中，新生儿瘦素管理导致下丘脑扩大，没有明显的神经心血管改变。雌性小鼠对新生儿生长限制或瘦素补充的影响不太敏感。总之，新生儿瘦素管理的影响调制的同时增长和性别。在生长受限的雄性小鼠中，生理性瘦素替代可改善成年神经心血管结局。
Premature delivery is often complicated by neonatal growth restriction and neurodevelopmental impairment. Because global over-nutrition increases the risk of adult metabolic syndrome, we sought a targeted intervention. Premature delivery and perinatal growth restriction decrease circulating levels of the neurotrophic hormone leptin. We hypothesized leptin supplementation would normalize the outcomes of mice with incipient neonatal growth restriction. Pups were fostered into litters of 6 or 12 to elicit divergent growth patterns. Pups in each litter received injections of saline or leptin from day 4–14. At 4 months, mice underwent tail cuff blood pressure measurement, behavioral testing and MRI. Mice fostered in litters of 12 had decreased weanling weights and leptin levels. Neonatal leptin administration normalized plasma leptin levels without influencing neonatal growth. Leptin replacement also normalized the hypertension, stress-linked immobility, conditioned fear, and amygdala enlargement seen in neonatal growth restricted male mice. In control males, neonatal leptin administration led to hypothalamic enlargement, without overt neurocardiovascular alterations. Female mice were less susceptible to the effects of neonatal growth restriction or leptin supplementation. In conclusion, the effects of neonatal leptin administration are modulated by concurrent growth and gender. In growth restricted male mice, physiologic leptin replacement improves adult neurocardiovascular outcomes.