Prenatal alcohol exposure delays the development of the cortical barrel field in neonatal rats.
Prenatal alcohol exposure delays the development of the cortical barrel field in neonatal rats.
复制标题
产前酒精暴露会延迟新生大鼠皮质桶状区域的发育。
DOI：
10.1007/s00221-005-0319-0
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发表时间：
2006
影响因子：
2
通讯作者：
Waters,RobertS
中科院分区：
文献类型：
--
作者：
Margret,CeciliaP;Li,ChengX;Chappell,TysonD;Elberger,AndreaJ;Matta,ShannonG;Waters,RobertS
子宫内酒精暴露产生感觉运动发育异常，通常持续到成年。我们利用与体表表征相关的啮齿动物皮质桶状场作为模型系统来研究产前酒精暴露（PAE）对早期体感觉皮质发育的影响。在本研究中，怀孕的雌性大鼠在怀孕的前20天每天灌胃高剂量酒精（6 gm/kg体重）。在妊娠第13天（G13）和20天（G20）测量了孕鼠的血液酒精水平。将乙醇处理组（EtOH）与正常对照（CF）组、营养配对（PF）组和交叉培养（XF）组进行比较。从G25（对应于出生后第2天（P2））到G32（对应于P9），所有治疗组的幼犬都检查了皮质桶发育。EtOH组和对照组幼犬称重、麻醉、灌注。大脑被切除并称重，小脑和嗅球被切除或不切除，新皮层被切除并称重。然后将皮质变平，切向切片，并用代谢标记物细胞色素氧化酶（CO）染色，以显示桶状区。桶体发育的进展分为三类：(a)不存在，(b)浑浊的桶状模式，和(c)形成良好的桶，中间有间隔。主要研究结果如下：(1) PAE使桶形野的发育延迟了1天或1天以上；(2)桶形野最初呈浑浊状，在随后的几天里转变为具有清晰分隔的间隔区域的成体样模式；(3)酒精组和对照组的桶形野在横向到内侧梯度上的发育不同；(4)53%的幼崽PAE使其出生延迟了1天或1天以上。(5)无论幼崽是在G23（非酒精对照组的正常预期出生日期）出生，还是在G27晚出生的酒精延迟幼崽的情况下，出生时都没有桶区，这表明产后经验对桶区发育的重要性；(6)PAE没有破坏正常的桶区模式，尽管全身和脑重量都受到损害。这些发现表明，PAE延缓了体感觉皮层（SI）的发育；这种延迟可能会干扰皮质回路的时间和形成。目前尚不清楚体感觉通路上的其他核是否也经历了类似的发育延迟，或者PAE是否选择性地破坏了皮质回路。
In-utero alcohol exposure produces sensorimotor developmental abnormalities that often persist into adulthood. The rodent cortical barrel field associated with the representation of the body surface was used as our model system to examine the effect of prenatal alcohol exposure (PAE) on early somatosensory cortical development. In this study, pregnant female rats were intragastrically gavaged daily with high doses of alcohol (6 gm/kg body weight) throughout the first 20 days of pregnancy. Blood alcohol levels were measured in the pregnant dams on gestational days 13 (G13) and G20. The ethanol treated group (EtOH) was compared to the normal control chowfed (CF) group, nutritionally matched pairfed (PF) group, and cross-foster (XF) group. Cortical barrel development was examined in pups across all treatment groups from G25, corresponding to postnatal day 2 (P2), to G32 corresponding to P9. The EtOH and control group pups were weighed, anesthetized, and perfused. Brains were removed and weighed with, and without cerebellum and olfactory bulbs, and neocortex was removed and weighed. Cortices were then flattened, sectioned tangentially, and stained with a metabolic marker, cytochrome oxidase (CO) to reveal the barrel field. Progression of barrel development was distinguished into three categories: (a) absent, (b) cloudy barrel-like pattern, and (c) well-formed barrels with intervening septae. The major findings are: (1) PAE delayed barrel field development by one or more days, (2) the barrel field first appeared as a cloudy pattern that gave way on subsequent days to an adult-like pattern with clearly demarcated intervening septal regions, (3) the barrel field developed differentially in a lateral-to-medial gradient in both alcohol and control groups, (4) PAE delayed birth by one or more days in 53% of the pups, (5) regardless of whether pups were born on G23 (normal expected birth date for non-alcohol controls) or as in the case for the alcohol-delayed pups born as late as G27, the barrel field was never present at birth suggesting the importance of postnatal experience on barrel field development, and (6) PAE did not disrupt the normal barrel field pattern, although both total body and brain weights were compromised. These findings suggest that PAE delays the development of the somatosensory cortex (SI); such delays may interfere with timing and formation of cortical circuits. It is unknown whether other nuclei along the somatosensory pathway undergo similar delays in development or if PAE selectively disrupts cortical circuitry.