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首页> 外文期刊>BMC Neuroscience >Brain size reductions associated with endothelin B receptor mutation, a cause of Hirschsprung’s disease
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Brain size reductions associated with endothelin B receptor mutation, a cause of Hirschsprung’s disease

机译：与内皮素B受体突变相关的脑大小减少，是Hirschsprung病的原因

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ETB has been reported to regulate neurogenesis and vasoregulation in foetal development. Its dysfunction was known to cause HSCR, an aganglionic colonic disorder with syndromic forms reported to associate with both small heads and developmental delay. We therefore asked, "is CNS maldevelopment a more general feature of ETB mutation?" To investigate, we reviewed the micro-CT scans of an?ETB?/? model animal, sl/sl rat, and quantitatively evaluated the structural changes of its brain constituents. Eleven neonatal rats generated from ETB /? cross breeding were sacrificed. Micro-CT scans were completed following 1.5% iodine-staining protocols. All scans were reviewed for morphological changes. Selected organs were segmented semi-automatically post-NLM filtering: TBr, T-CC, T-CP, OB, Med, Cer, Pit, and S&I Col. Volumetric measurements were made using Drishti rendering software. Rat genotyping was completed following analysis. Statistical comparisons on organ volume, organ growth rate, and organ volume/bodyweight ratios were made between sl/sl and the control groups based on autosomal recessive inheritance. One-way ANOVA was also performed to evaluate potential dose-dependent effect. sl/sl rat has 16.32% lower body weight with 3.53% lower growth rate than the control group. Gross intracranial morphology was preserved in sl/sl rats. However, significant volumetric reduction of 20.33% was detected in TBr; similar reductions were extended to the measurements of T-CC, T-CP, OB, Med, and Pit. Consistently, lower brain and selected constituent growth rates were detected in sl/sl rat, ranging from 6.21% to 11.51% reduction. Lower organ volume/bodyweight ratio was detected in sl/sl rats, reflecting disproportional neural changes with respect to body size. No consistent linear relationships exist between ETB copies and intracranial organ size or growth rates. Although ETB?/? mutant has a normal CNS morphology, significant size reductions in brain and constituents were detected. These structural changes likely arise from a combination of factors secondary to dysfunctional ET-1/ET-3/ETB signalling, including global growth impairment from HSCR-induced malnutrition and dysregulations in the neurogenesis, angiogenesis, and cerebral vascular control. These changes have important clinical implications, such as autonomic dysfunction or intellectual delay. Although further human study is warranted, our study suggested comprehensive managements are required for HSCR patients, at least in ETB?/? subtype.
机译：据报道，ETB规范胎儿发育中的神经发生和血管瘤。已知其功能障碍引起HSCR，一种与综合组织形式的Aganglionic结肠疾病报告为与小头和发育延迟相关联。因此，我们被问到，“CNS Maldevelopment是ETB变异的更一般特征吗？”要调查，我们审查了etb的微型CT扫描？/？模型动物，SL / SL大鼠，并定量评估其脑成分的结构变化。来自ETB的11个新生大鼠/？牺牲了交叉育种。在1.5％碘染色方案后完成微型CT扫描。所有扫描都审查了形态学变化。选择的器官被分段半自动后NLM过滤：使用DRISHTI渲染软件进行TBR，T-CC，T-CP，OB，MED，CER，PIT和S＆I CL.体积测量。在分析后完成大鼠基因分型。基于常染色体隐性遗传，在SL / SL和对照组之间进行器官体积，器官生长速率和器官体重比对器官体积，器官生长速率和器官/体重比的统计学比较。还进行单向ANOVA以评估潜在的剂量依赖性效果。 SL / SL大鼠的体重较低16.32％，增长率低3.53％，比对照组较低。在SL / SL大鼠中保存了总颅内形态。然而，在TBR中检测到显着的体积减少20.33％;与T-CC，T-CP，OB，MED和坑的测量相似，延伸了类似的还原。始终如一地，在SL / SL大鼠中检测降低脑和选定的组成生长速率，从减少6.21％至11.51％。在SL / SL大鼠中检测到较低的器官体积/体重比，反映了相对于体尺寸的化学神经变化。在ETB复制和颅内器官尺寸或生长速率之间没有一致的线性关系。虽然etb？/？突变体具有正常的CNS形态，检测到脑和成分的大小减少。这些结构变化可能来自次官能障碍ET-1 / ET-3 / ETB信号传导的因素的组合，包括来自HSCR诱导的营养不良和神经发生，血管生成和脑血管控制中的全球生长损伤。这些变化具有重要的临床意义，例如自主功能障碍或智力延迟。虽然需要进一步进行人类研究，但我们的研究表明HSCR患者需要综合管理，至少在ETB中？/？亚型。

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