title: Effects of nerve growth factor on splenic norepinephrine and pineal N-acetyl-transferase in neonate rats exposed to alcohol in utero: neuroimmune correlates.
abstract: Prenatal alcohol exposure (FAE) has been associated with multiple anomalies, including a selective developmental delay of sympathetic innervation in lymphoid organs. Sympathetic neurons require nerve growth factor (NGF) for their development and maintenance, and recent evidence has suggested that alcohol impairs the synthesis and/or biological activity of NGF in selected central and peripheral neurons. Thus, the present study examined the hypothesis that NGF administration to FAE rats during early postnatal development would reverse some of the peripheral sympathetic deficits. Neonate rats, FAE and the corresponding control cohorts, received daily treatments of NGF or cytochrome C (0.3 mg/kg; s.c.) for various time intervals, and were killed 24 hr or 10 days after the last treatment. The measured parameters included norepinephrine (NE) concentrations in the spleen and heart, which receive nor-adrenergic innervation from the coeliac ganglion and the superior cervical ganglion (SCG), respectively. In addition, we measured the activity of pineal N-acetyltransferase (NAT), the rate-limiting enzyme of melatonin biosynthesis, which depends on sympathetic innervation from the SCG. The data show that chronic, but not acute, NGF treatments reversed the FAE-related deficits in splenic NE concentrations as well as in pineal NAT activity in a time- and age-dependent manner. Sympathetic neurons play an important role in immune modulation. Thus, the altered splenic NE levels and pineal NAT activity may play a role in immune deficits associated with exposure to alcohol in utero.
authors.affiliation: Department of Neurobiology and Anatomy, University of Texas Medical School, Houston, USA. zehavag@nbal-9.med.uth.tmc.edu
authors.forename: Z
authors.initials: Z
authors.lastname: Gottesfeld
authors.forename: S
authors.initials: S
authors.lastname: Simpson
authors.forename: A
authors.initials: A
authors.lastname: Yuwiler
authors.forename: J R
authors.initials: JR
authors.lastname: Perez-Polo
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001191:Arylamine N-Acetyltransferase / Q000378:metabolism*; D002492:Central Nervous System Depressants / Q000633:toxicity*; D003574:Cytochrome c Group / Q000378:metabolism; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D009206:Myocardium / Q000201:enzymology; D009414:Nerve Growth Factors / Q000494:pharmacology*; D015213:Neuroimmunomodulation / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism*; D010870:Pineal Gland / Q000187:drug effects / Q000196:embryology / Q000201:enzymology*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*
chemical_list: D002492:Central Nervous System Depressants; D003574:Cytochrome c Group; D009414:Nerve Growth Factors; D000431:Ethanol; D001191:Arylamine N-Acetyltransferase; D009638:Norepinephrine