Choline supplementation prevents the effects of bilirubin on cerebellar-mediated behavior in choline-restricted Gunn rat pups.
Choline supplementation prevents the effects of bilirubin on cerebellar-mediated behavior in choline-restricted Gunn rat pups.
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DOI：
10.1038/s41390-020-01187-7
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发表时间：
2021-05
影响因子：
3.6
通讯作者：
Bearer CF
中科院分区：
文献类型：
--
作者：
Waddell J;Rickman NC;He M;Tang N;Bearer CF
胆红素是由血红蛋白分解产生的，通常被分解代谢并排出体外。血清胆红素神经毒性蓄积常发生于早产儿。纯合的古恩大鼠缺乏尿苷二磷酸-葡萄糖醛酸转移酶-1A 1（UGT 1A 1），这是生物转化胆红素所需的酶。这种高胆红素血症的啮齿动物模型模拟了在人类婴儿中观察到的胆红素毒性的许多方面。我们证明，在出生后早期发育中补充胆碱对胆碱限制的古恩大鼠在出生后第5天诱导高胆红素血症时具有神经保护作用。我们首先比较了行为和小脑的重量所生的母鼠消耗定期大鼠饲料的母鼠消耗胆碱限制饮食。其次，我们测量的行为和小脑重量的幼仔出生胆碱限制的大坝，饲养胆碱限制的饮食，补充或不补充胆碱和治疗或不磺胺二甲氧嘧啶（SDMX）。胆碱限制饮食没有改变行为结果，但无论基因型或SDMX管理，胆碱限制组的小脑重量减少。SDMX在JJ幼鼠中引起行为缺陷，胆碱补充剂改善了SDMX治疗的JJ大鼠的大多数行为效应和小脑重量。提示胆碱可作为一种安全、有效的神经保护性干预措施，预防胆碱缺乏早产儿高胆红素血症。
Bilirubin is produced by the breakdown of hemoglobin, and is normally catabolized and excreted. Neurotoxic accumulation of serum bilirubin often occurs in premature infants. The homozygous Gunn rat lacks uridine diphosphate-glucuronosyltransferase-1A1 (UGT1A1), the enzyme needed to biotransform bilirubin. This rodent model of hyperbilirubinemia emulates many aspects of bilirubin toxicity observed in the human infant. We demonstrate that choline supplementation in early postnatal development is neuroprotective in the choline restricted Gunn rat, when hyperbilirubinemia is induced on postnatal day 5. We first compared behaviors and cerebellar weight of pups born to dams consuming regular rat chow to those of dams consuming choline-restricted diets. Secondly, we measured behaviors and cerebellar weights of pups born to choline-restricted dams, reared on a choline-restricted diet, supplemented with or without choline and treated with or without sulfadimethoxine (SDMX). A choline-restricted diet did not change the behavioral outcomes, but cerebellar weight was reduced in the choline-restricted group regardless of genotype or SDMX administration. SDMX induced behavioral deficits in jj pups, and choline supplementation improved most behavioral effects and cerebellar weight in SDMX-treated jj rats. These results suggest that choline may be used as a safe and effective neuroprotective intervention against hyperbilirubinemia in the choline deficient premature infant.
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影响因子：
4.2
作者：
HAMM, RJ;PIKE, BR;JENKINS, LW
通讯作者：
JENKINS, LW
影响因子：
4.2
作者：
Niculescu, MD;Zeisel, SH
通讯作者：
Zeisel, SH
影响因子：
5
作者：
Bernhard, Wolfgang;Full, Anna;Franz, Axel R.
通讯作者：
Franz, Axel R.
影响因子：
3.7
作者：
Gallego-Ortega D;Ramirez de Molina A;Ramos MA;Valdes-Mora F;Barderas MG;Sarmentero-Estrada J;Lacal JC
通讯作者：
Lacal JC
DOI：
10.1001/archpedi.1959.02070010593009
发表时间：
1959-01-01
期刊：
AMA JOURNAL OF DISEASES OF CHILDREN
影响因子：
--
作者：
JOHNSON, L;SARMIENTO, F;DAY, R
通讯作者：
DAY, R