Margret Cecilia P, Li Cheng X, Elberger Andrea J, Matta Shannon G, Chappell Tyson D, Waters Robert S
Department of Anatomy and Neurobiology, University of Tennessee Health Science Center College of Medicine, 855 Monroe Avenue, Memphis, TN 38163, USA.
Exp Brain Res. 2005 Aug;165(2):167-78. doi: 10.1007/s00221-005-2287-9. Epub 2005 Apr 22.
Maternal alcohol exposure results in a variety of neurodevelopmental abnormalities that include cognitive and sensorimotor dysfunctions that often persist into adulthood. Many reports of central nervous system disturbances associated within a clinical diagnosis of fetal alcohol syndrome point toward disturbances in central information processing. In this study, we used the rat barrel field cortex as a model system to examine the effects of prenatal alcohol exposure (PAE) on the organization and size of the large whisker representation in layer IV of the posteromedial barrel subfield (PMBSF) in somatosensory cortex. Pregnant rats (Sprague-Dawley) were intragastrically gavaged daily with alcohol doses (6 gm/kg body weight) from gestational day 1 to day 20 in a chronic binge pattern which produced blood alcohol levels ranging between 260 mg/dl and 324 mg/dl. Chow-fed (CF), pair-fed (PF), and cross-foster (XF) groups served as normal, nutritionally matched, and maternal controls, respectively, for the ethanol-exposed (EtOH) treatment group. All pups were examined on gestational day 32 corresponding approximately to postnatal day 9. EtOH and control group pups were weighed, anesthetized, and perfused. Brains were removed and weighed, with and without cerebellum and olfactory bulbs, and the neocortex was removed and weighed. Cortices were then flattened, sectioned tangentially, and stained with a metabolic marker-cytochrome oxidase-to reveal the barrel field. A subset of 27 cortical barrels, associated with the representation of the large whisker pad, was selected to examine in detail. The major results were: (i) the total barrel field area comprising the PMBSF was significantly reduced in EtOH (by 17%) and XF (by 16%) pups compared with CF pups, (ii) the sizes of individual barrels within the PMBSF were also significantly reduced in EtOH (16%) and XF (18%) pups, (iii) the septal region between barrels was also significantly reduced in EtOH (18%) and XF (12%) pups, (iv) anteriorly located barrels underwent greater reduction in size relative to the posteriorly located barrels, (v) body weights were also significantly reduced in EtOH (21%) and XF (27%) pups, (vi) total brain weight [with and without (forebrain) cerebellum/olfactory bulbs] and cortical weights were also significantly reduced in EtOH (total brain weight 15%, forebrain weight 16%, cortical weight 15%) and XF (18%, 19%, 20%) pups, and in contrast (vi) neither the overall barrel field pattern nor the pattern of individual barrels in the PMBSF was altered. These findings suggest that PAE reduces body and brain weight as well as the central cortical representation of the whisker pad, while leaving the overall barrel field pattern unperturbed. While these results might appear to support a miniaturization hypothesis (smaller PMBSF, smaller brain, smaller body weight), PAE also shows regional vulnerability within the PMBSF whereby anteriorly located barrels are most affected.
母体酒精暴露会导致多种神经发育异常,包括认知和感觉运动功能障碍,这些障碍常常会持续到成年期。许多与胎儿酒精综合征临床诊断相关的中枢神经系统紊乱报告都指向中枢信息处理方面的紊乱。在本研究中,我们使用大鼠桶状皮质作为模型系统,来研究产前酒精暴露(PAE)对体感皮质后内侧桶状亚区(PMBSF)第IV层中大型触须表征的组织和大小的影响。怀孕的大鼠(斯普拉格-道利大鼠)从妊娠第1天到第20天每天以慢性暴饮模式经胃内灌胃给予酒精剂量(6克/千克体重),这会使血液酒精水平在260毫克/分升和324毫克/分升之间。自由摄食(CF)、配对喂养(PF)和交叉寄养(XF)组分别作为乙醇暴露(EtOH)治疗组的正常、营养匹配和母体对照。所有幼崽在妊娠第32天进行检查,这大约对应于出生后第9天。对EtOH组和对照组的幼崽进行称重、麻醉和灌注。取出大脑并称重,包括有和没有小脑及嗅球的情况,然后取出新皮质并称重。接着将皮质展平,进行切线切片,并用代谢标记物细胞色素氧化酶染色以显示桶状皮质区。选择了与大型触须垫表征相关的27个皮质桶的子集进行详细检查。主要结果如下:(i)与CF组幼崽相比,EtOH组(减少17%)和XF组(减少16%)幼崽中包含PMBSF的整个桶状皮质区面积显著减小;(ii)PMBSF内单个桶的大小在EtOH组(减少16%)和XF组(减少18%)幼崽中也显著减小;(iii)EtOH组(减少18%)和XF组(减少12%)幼崽中桶之间的间隔区域也显著减小;(iv)相对于后部的桶,前部的桶尺寸减小得更大;(v)EtOH组(减少21%)和XF组(减少27%)幼崽的体重也显著降低;(vi)EtOH组(全脑重量减少15%,前脑重量减少16%,皮质重量减少15%)和XF组(分别减少18%、19%、20%)幼崽的全脑重量[包括有和没有(前脑)小脑/嗅球的情况]和皮质重量也显著降低,而与之形成对比的是(vi)PMBSF的整体桶状皮质区模式和单个桶的模式均未改变。这些发现表明,PAE会降低体重和脑重以及触须垫的中央皮质表征,同时使整体桶状皮质区模式不受干扰。虽然这些结果似乎支持一种小型化假说(较小的PMBSF、较小的脑、较小的体重),但PAE也显示出PMBSF内的区域易损性,其中前部的桶受影响最大。