Litter size reduction accentuates maternal care and alters behavioral and physiological phenotypes in rat adult offspring

Litter size reduction accentuates maternal care and alters behavioral and physiological phenotypes in rat adult offspring
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DOI:
10.1007/s12576-018-0594-8
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发表时间:
2018-11-01
影响因子:
2.3
通讯作者:
Giusti-Paiva, Alexandre
Giusti-Paiva, Alexandre
中科院分区:
医学4区
文献类型:
--
作者:
Enes-Marques, Silvia;Giusti-Paiva, Alexandre

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母性行为对幼崽的行为、内分泌和神经发育有很大的影响。这项研究调查了通过改变胎仔大小来改变新生儿营养环境对成年大鼠的母婴护理以及焦虑和恐惧样行为的影响。在出生后第2天(PND),每窝调整为每母猪3只的小窝大小(SL)或每只母猪12只的正常窝大小(NL)。哺乳期间每天对母体行为进行评分(PND2-21)。对子代大鼠的体重增加、摄食量、肥胖度和生化指标进行评估。对PND60进行旷场测试、高架正迷宫(EPM)测试和恐惧条件反射实验。胎仔数量的减少加强了哺乳大鼠的母爱,增加了弓背姿势和舔幼崽的能力。SL后代成年后体重增加加快、吞噬增多、内脏脂肪量增加、血脂异常和高瘦素血症。与NL相比,两性SL后代在开阔的野外表现出更强的抗思维能力,在EPM中表现出完整的焦虑表型,而在恐惧条件反射测试中所花费的冻结时间减少。由胎仔大小决定的新生儿环境对成年动物的代谢表型以及对应激刺激的行为反应起着至关重要的作用,并对类焦虑和恐惧行为产生影响。后代的这些行为变化可能至少在一定程度上是母亲增加照顾的结果。
Maternal behavior has a substantial impact on the behavioral, endocrine, and neural development of the pups. This study investigated the effect of altering the neonatal nutritional environment by modifying the litter size on maternal care and anxiety- and fear-like behaviors in rats during adulthood. On postnatal day (PND) 2, litters were adjusted to a small litter (SL) size of three pups per dam or normal litter (NL) size of 12 pups per dam. Maternal behaviors were scored daily during lactation (PND2-21). The weight gain, food intake, adiposity, and biochemical landmarks of offspring rats were evaluated. On PND60, performances in the open field, elevated plus-maze (EPM), and fear conditioning test were measured. The reduction of the litter size enhanced maternal care in lactating rats, increasing the arched-back posture and licking pups. SL offspring exhibited accelerated weight gain, hyperphagia, increased visceral fat mass, dyslipidemia, and hyperleptinemia in adulthood. The SL offspring of both sexes showed an increase in the anti-thigmotactic effect in the open field, an intact anxious-phenotype in the EPM, and a decrease in the time spent freezing during the fear-conditioning test, compared to NL. The neonatal environment as determined by litter size plays a crucial role in programming the adult metabolic phenotype as well as behavioral responses to stressful stimuli, with an impact on anxiety-like and fear behaviors. These behavioral changes in offspring may be, at least in part, a result of increased maternal care.