Annie M. Cameron

Nutritional Influences on Adrenal Chromaffin Cell Development: Comparison with Central Neurons

ABSTRACT: Neurotransmitter systems in the developing brain are generally protected from growth retardation associated with nutritional deprivation. To investigate if such protective mechanisms extend to similar tissues in the peripheral sympathetic system, maturation of the chromaffin cells of the adrenal medulla and development of their centrally derived splanchnic innervation were evaluated in rats whose nutritional status had been altered during the neonatal period by increasing (16–17 pups/litter) or decreasing (five to six pups/litter) the litter size from the standard (11–12 pups/litter). Ontogeny of adrenal catecholamine stores and activities of catecholamine-biosynthetic enzymes tyrosine hydroxylase and phenylethanolamine N-methyltransferase were monitored, along with activity of choline acetyltransferase, a marker enzyme for the preganglionic neurons innervating the chromaffin cells. Neonatal nutritional deprivation slowed body weight gain and retarded development of the chromaffin cells, as evidenced by subnormal catecholamine stores, tyrosine hydroxylase and phenylethanolamine N-methyltransferase activities. The effects persisted despite the complete recovery of body weights postweaning. The developmental alterations were not caused by overcrowding stress, as plasma corticosterone levels were not elevated in the large litter group. Neonatal nutritional enrichment promoted body weight gain but failed to enhance development of adrenal catecholamines; tyrosine hydroxylase and phenylethanolamine N-methyltransferase activities were elevated only in the preweaning period. In contrast to effects on the chromaffin cells, altered neonatal nutritional status had only minor, transient effects on the development of the centrally derived cholinergic innervation of the adrenal and produced only small changes (<10%) in brain tyrosine hydroxylase activity. These results suggest that, unlike central transmitter systems, maturation of chromaffin cells is adversely affected by neonatal nutritional deprivation; ontogenetic gains may already be close to optimum at normal nutritional status.

Effects of prenatal nitrofen exposure on cardiac structure and function in the rat

The herbicide nitrofen was administered to pregnant Fischer-344 and Sprague-Dawley rats on Days 10-13 of gestation (po, 20 or 40 mg/kg daily) and its effects on cardiac structure and function were investigated in the offspring. In the 21-day fetuses, nitrofen did not influence intrauterine growth or basal heart rate. In contrast, the herbicide produced a marked depression of heart rate and abnormal electrocardiographic (ECG) profiles in the newborn rats, in conjunction with labored respiratory movements and a profound increase in postnatal mortality. A few animals displayed cardiac ventricular septal defects and diaphragmatic hernias but these malformations did not appear to be associated with the ECG changes. The chronotropic deficiencies seen in the nitrofen-treated pups were reversible by acute hyperoxia (40% oxygen). These results suggest that the teratogenic effects of nitrofen on cardiac physiology and on postnatal mortality cannot be accounted for solely by specific gross anatomical damages to the rat heart and diaphragm; rather, other more subtle morphological and physiological factors which contribute to improper systemic delivery and cellular utilization of oxygen may be involved.

Teratogenic effects of nitrofen on cellular and functional maturation of the rat lung

The herbicide nitrofen was administered to pregnant Sprague-Dawley and Fischer-344 rats on Days 10-13 of gestation (po, 20 or 40 mg/kg daily) and the effects of maturation of the perinatal lung were evaluated. Nitrofen interfered with the ontogenetic acquisition of lung cells as DNA, RNA, and protein content were subnormal. The hypoplastic lungs in the newborns were associated with structural deficits, resulting in a profound reduction of surface area available for gas exchange and depressed lung compliance. Other factors which influence pulmonary function and systemic delivery of oxygen were also considered. Adrenal catecholamines, which play an important role in surfactant production and fluid resorption in the lung during the transition to air-breathing, were markedly reduced. In addition, red blood cell concentration was significantly diminished. Taken together, these results suggest that the neonatal mortality observed in the nitrofen-treated rats is likely associated with respiratory distress caused by a number of cellular and functional aberrations. These include (a) hypoplasia and structural defects in the lung leading to deficient pulmonary function, (b) deficits in adrenal catecholamines potentially impeding the transition of the lung to air-breathing, and (c) impaired systemic delivery of oxygen due to reduced hemoglobin concentration.

Trophic control of the ornithine decarboxylase/polyamine system in neonatal rat brain regions: lesions caused by 6-hydroxydopamine produce effects selective for cerebellum

Norepinephrine has been hypothesized as a trophic factor influencing postnatal development of the cerebellum. In the current study, neonatal rats were given 6-hydroxydopamine (6-OHDA) to destroy noradrenergic projections and the effects on the ornithine decarboxylase (ODC)/polyamine system were evaluated; ODC initiates the synthesis of polyamines, which are known to control cellular development in the cerebellum, and neonatal ODC activity is regulated in part by beta 2-adrenergic receptors. Intracisternal administration of 6-OHDA resulted in complete and permanent depletion of cerebellar norepinephrine and a deficit in ODC, polyamine levels and cerebellar growth. Subcutaneous administration of 6-OHDA, which caused only a small initial reduction in cerebellar norepinephrine, did not affect ODC and had only minor effects on tissue growth. Indeed, levels of the polyamines tended to be elevated after subcutaneous 6-OHDA, associated with postweaning elevations in norepinephrine, results which are probably indicative of axonal regeneration. In contrast to the effects of 6-OHDA on cerebellar development, neither the intracisternal nor subcutaneous drug treatment had any effect on cerebral cortical polyamines or growth, although the intracisternal treatment did impair ODC activity early in development. These data suggest that postnatal noradrenergic input, acting through the ODC/polyamine pathway, plays a selective role in cerebellar development.