White L D, Lawson E E
Department of Pediatrics, University of North Carolina, Chapel Hill 27599, USA.
Pediatr Res. 1997 Oct;42(4):455-62. doi: 10.1203/00006450-199710000-00006.
Catecholamines are a class of neurotransmitters involved in central nervous system autonomic control. Both acute and chronic hypoxia create alterations in ventilation and blood pressure via catecholamine release, although the mechanisms of these alterations are unknown. The enzymes tyrosine hydroxylase (TH) and phenylethanolamine N-methyltransferase (PNMT) catalyze the rate-limiting step in the catecholamine pathway and production of epinephrine, respectively. Both have been colocalized with Fos protein in metabolic mapping studies of the O2-chemosensory pathway of adult and early postnatal rat. Thus, catecholamines are putative neurotransmitters in a subset of second and higher order respiratory neurons. To characterize the effects of prenatal hypoxia on subsequent TH and PNMT gene and protein expression, pregnant rats were placed in moderate hypoxia (10% O2) from gestational d 18 until birth. Northern and Western analyses of dorsal (catecholaminergic/adrenergic cell group 2) and ventral (catecholaminergic/adrenergic cell group 1) medullary tissue of postnatal (P) age P0, P3, P7, P10, and P14 pups were then done to examine changes in TH and PNMT mRNA and protein compared with normoxia-reared controls. Compared with controls, pups exposed to maternal hypoxia during pregnancy had lower levels of TH mRNA and protein at birth in dorsal medulla and higher levels of TH mRNA the first postnatal week in the ventral medulla. Pups that had been hypoxic in utero showed significantly lower levels of PNMT protein during the second postnatal week in dorsal medulla than did controls. Prenatal hypoxia-induced changes in levels of enzymes responsible for catecholamine synthesis may later be manifest as developmental deficiencies in neuronal function. This may compromise responses to acute hypoxic challenges during early postnatal life and contribute to autonomic nervous system disorders of the newborn such as apnea and sudden infant death syndrome.
儿茶酚胺是一类参与中枢神经系统自主控制的神经递质。急性和慢性缺氧均可通过儿茶酚胺释放引起通气和血压改变，尽管这些改变的机制尚不清楚。酪氨酸羟化酶（TH）和苯乙醇胺N-甲基转移酶（PNMT）分别催化儿茶酚胺途径中的限速步骤和肾上腺素的生成。在成年和出生后早期大鼠的O2化学感受途径的代谢图谱研究中，二者均与Fos蛋白共定位。因此，儿茶酚胺被认为是第二级及更高级呼吸神经元亚群中的神经递质。为了表征产前缺氧对随后TH和PNMT基因及蛋白表达的影响，将怀孕大鼠从妊娠第18天至出生置于中度缺氧（10% O2）环境中。然后对出生后（P）第0、3、7、10和14天幼崽的背侧（儿茶酚胺能/肾上腺素能细胞群2）和腹侧（儿茶酚胺能/肾上腺素能细胞群1）髓质组织进行Northern和Western分析，以检查与常氧饲养对照相比TH和PNMT mRNA及蛋白的变化。与对照相比，孕期暴露于母体缺氧的幼崽出生时背侧髓质中TH mRNA和蛋白水平较低，而腹侧髓质在出生后第一周TH mRNA水平较高。子宫内缺氧的幼崽在出生后第二周背侧髓质中PNMT蛋白水平明显低于对照。产前缺氧引起的儿茶酚胺合成相关酶水平变化可能随后表现为神经元功能发育缺陷。这可能会损害出生后早期对急性缺氧挑战的反应，并导致新生儿自主神经系统疾病，如呼吸暂停和婴儿猝死综合征。
