PERSISTENT ALTERATIONS IN REGIONAL BRAIN GLIAL FIBRILLARY ACIDIC PROTEIN AND SYNAPTOPHYSIN LEVELS FOLLOWING PRENATAL AND POSTNATAL POLYCHLORINATED BIPHENYL EXPOSURE

Pregnant Wistar WU rats were exposed to 0, 5, and 25 mg of the commerc ial polychlorinated biphenyl (PCB) mixture Aroclor 1254 per kilogram o f body weight on Days 10 to 16 of gestation, Pregnant rats were sacrif iced on Gestation Day 20 to observe effects on fetal body and brain we ights. Male and female offspring were sacrificed on Postnatal Days 21 and 90 (PND21 and PND90, respectively) and examined for treatment-rela ted effects on neurochemical parameters, The concentrations of the neu ronal and glial cell markers, synaptophysin and glial fibrillary acidi c protein (GFAP), were measured in diverse brain regions from the offs pring using immunochemical techniques. The level of calcineurin (a cal modulin-regulated protein phosphatase) activity was measured in cerebe llar homogenates. In addition, ethoxyresorufin O-deethylase (EROD) act ivity was determined in hepatic microsomes as a measure of a well-char acterized response to PCB exposure in experimental animals, The major alterations of GFAP levels following maternal PCB treatment were signi ficant increases in the lateral olfactory tract (LOT) and the cerebell um (CB) and significant decreases in the brain stem (BS) of the offspr ing on PND21 and 90. Synaptophysin levels were significantly decreased relative to controls in the LOT, prefrontal cortex, and striatum of t he offspring on PND90. In the BS, synaptophysin levels were significan tly decreased relative to controls in male and female weanlings on PND 21 and males on PND90; however, significant increases were observed in the BS of females on PND90. No effect of maternal PCB treatment was o bserved on levels of GFAP and synaptophysin in the dorsal hippocampus on PND21 and 90. Due to analytical restrictions statistical comparison s of GFAP levels were limited to examining the effect of maternal PCB treatment per brain region per sex per time point, Calcineurin activit y was decreased in the female CB on PND21, but a significant increase in activity was observed in the female CB on PND90. No effect of mater nal PCB treatment was observed on the cerebellar calcineurin activity in male offspring on PND21 and 90. EROD activity was highly induced in maternal microsomes from both PCB treatment groups, but only slightly induced in fetal hepatic microsomes. On PND21 weanling hepatic micros omal EROD activity was highly induced following gestational and lactat ional PCB exposure; however, on PND90 EROD activity was unaffected by maternal PCB treatment in male offspring and significantly decreased i n female offspring. The results of the present study indicate that ges tational and lactational exposure to the commercial PCB mixture result s in long-term alterations in a neuronal and glial cell markers in spe cific brain regions of rats. These marker proteins may be useful for d etermining the structure-activity relationships in PCB-induced develop mental neurotoxicity. (C) 1996 Academic Press, Inc.