Radlowski Emily C, Conrad Matthew S, Lezmi Stephane, Dilger Ryan N, Sutton Brad, Larsen Ryan, Johnson Rodney W
Department of Animal Sciences, University of Illinois, Urbana, Illinois, United States of America; Division of Nutritional Sciences, University of Illinois, Urbana, Illinois, United States of America.
Neuroscience Program, University of Illinois, Urbana, Illinois, United States of America.
PLoS One. 2014 Mar 17;9(3):e91951. doi: 10.1371/journal.pone.0091951. eCollection 2014.
The piglet was investigated as a potential model for studying brain and cognitive deficits associated with being born small for gestational age (SGA). Naturally farrowed SGA (0.7-1.0 kg BW) and average for gestational age (AGA, 1.3-1.6 kg BW) piglets were obtained on postnatal day (PD) 2, placed in individual cages, and provided a nutritionally adequate milk replacer diet (285 ml/kg/d). Beginning at PD14, performance in a spatial T-maze task was assessed. At PD28, piglets were anesthetized for magnetic resonance (MR) imaging to assess brain structure (voxel-based morphometry), connectivity (diffusion-tensor imaging) and metabolites in the hippocampus and corpus callosum (proton MR spectroscopy). Piglets born SGA showed compensatory growth such that BW of SGA and AGA piglets was similar (P>0.05), by PD15. Birth weight affected maze performance, with SGA piglets taking longer to reach criterion than AGA piglets (p<0.01). Total brain volume of SGA and AGA piglets was similar (P<0.05), but overall, SGA piglets had less gray matter than AGA piglets (p<0.01) and tended to have a smaller internal capsule (p = 0.07). Group comparisons between SGA and AGA piglets defined 9 areas (≥ 20 clusters) where SGA piglets had less white matter (p<0.01); 2 areas where SGA piglets had more white matter (p<0.01); and 3 areas where SGA piglets had more gray matter (p<0.01). The impact of being born SGA on white matter was supported by a lower (p<0.04) fractional anisotropy value for SGA piglets, suggesting reduced white matter development and connectivity. None of the metabolites measured were different between groups. Collectively, the results show that SGA piglets have spatial learning deficits and abnormal development of white matter. As learning deficits and abnormalities in white matter are common in SGA human infants, the piglet is a tractable translational model that can be used to investigate SGA-associated cognitive deficits and potential interventions.
该仔猪被作为一种潜在模型，用于研究与小于胎龄出生（SGA）相关的脑和认知缺陷。在出生后第2天（PD2）获得自然分娩的SGA（体重0.7 - 1.0千克）和适于胎龄（AGA，体重1.3 - 1.6千克）的仔猪，将其置于单独的笼中，并提供营养充足的代乳粉日粮（285毫升/千克/天）。从PD14开始，评估其在空间T迷宫任务中的表现。在PD28时，对仔猪进行麻醉以进行磁共振（MR）成像，评估脑结构（基于体素的形态学测量）、连通性（扩散张量成像）以及海马体和胼胝体中的代谢物（质子MR波谱分析）。出生时为SGA的仔猪表现出代偿性生长，到PD15时，SGA和AGA仔猪的体重相似（P>0.05）。出生体重影响迷宫表现，SGA仔猪达到标准所需时间比AGA仔猪长（p<0.01）。SGA和AGA仔猪的全脑体积相似（P<0.05），但总体而言，SGA仔猪的灰质比AGA仔猪少（p<0.01），且内囊往往较小（p = 0.07）。SGA和AGA仔猪之间的组间比较确定了9个区域（≥20个簇），SGA仔猪在这些区域的白质较少（p<0.01）；2个区域SGA仔猪的白质较多（p<0.01）；3个区域SGA仔猪的灰质较多（p<0.01）。SGA仔猪白质分数各向异性值较低（p<0.04），这支持了出生时为SGA对白质的影响，表明白质发育和连通性降低。两组之间所测量的代谢物均无差异。总体而言，结果表明SGA仔猪存在空间学习缺陷和白质发育异常。由于学习缺陷和白质异常在SGA人类婴儿中很常见，仔猪是一种易于处理的转化模型，可用于研究与SGA相关的认知缺陷及潜在干预措施。
