EFFECTS OF ETHANOL ON DEVELOPMENT OF LOCUS-COERULEUS BRAIN-STEM TRANSPLANTS IN OCULO

In this investigation, we studied the effects of ethanol (EtOH) on the development of noradrenergic (NE) neurons of the locus coeruleus. Fet al brainstem tissue from embryonic days 15-17 was grafted into the ant erior chamber of the eye of adult rats. Two different experimental gro ups were exposed to 16% EtOH in the drinking water during different de velopmental windows. The first group received EtOH 24 h after transpla ntation and during the whole experimental period of 7 weeks (continuou s EtOH), and the second group only during the last 5 weeks of the expe rimental period (delayed EtOH). The control group received water ad li bitum. After 7 weeks, all the animals were sacrificed and morphologica l evaluations were performed. Immunohistochemical analysis showed that axon bundle formation and NE fiber outgrowth into the host iris was s ignificantly reduced in the continuous EtOH-treated group compared to controls. We also studied the morphology of TH-positive neurons and pr ocesses in the intraocular transplants. A significant decrease in TH-p ositive staining intensity was observed in the continuous EtOH-treated group compared to controls. Moreover, we found a significant decrease in cell size and neuronal survival in both EtOH-treated groups compar ed to controls. The present results suggest that chronic EtOH exposure during development leads to an altered axonal outgrowth and decreased cell sizes and number of NE neurons in intraocular brain stem grafts. Furthermore, we found that NE neurons are more sensitive to EtOH expo sure during the last prenatal days and the first postnatal week of dev elopment, compared to a later developmental period. (C) 1998 Academic Press.