Persistent alterations in regional brain glial fibrillary acidic protein and synaptophysin levels following pre- and postnatal polychlorinated biphenyl exposure.
Pregnant Wistar WU rats were exposed to 0, 5, and 25 mg of the commercial polychlorinated biphenyl (PCB) mixture Aroclor 1254 per kilogram of body weight on Days 10 to 16 of gestation. Pregnant rats were sacrificed on Gestation Day 20 to observe effects on fetal body and brain weights. Male and female offspring were sacrificed on Postnatal Days 21 and 90 (PND21 and PND90, respectively) and examined for treatment-related effects on neurochemical parameters. The concentrations of the neuronal and glial cell markers, synaptophysin and glial fibrillary acidic protein (GFAP), were measured in diverse brain regions from the offspring using immunochemical techniques. The level of calcineurin (a calmodulin-regulated protein phosphatase) activity was measured in cerebellar homogenates. In addition, ethoxyresorufin O-deethylase (EROD) activity was determined in hepatic microsomes as a measure of a well-characterized response to PCB exposure in experimental animals. The major alterations of GFAP levels following maternal PCB treatment were significant increases in the lateral olfactory tract (LOT) and the cerebellum (CB) and significant decreases in the brain stem (BS) of the offspring on PND21 and 90. Synaptophysin levels were significantly decreased relative to controls in the LOT, prefrontal cortex, and striatum of the offspring on PND90. In the BS, synaptophysin levels were significantly decreased relative to controls in male and female weanlings on PND21 and males on PND90; however, significant increases were observed in the BS of females on PND90. No effect of maternal PCB treatment was observed on levels of GFAP and synaptophysin in the dorsal hippocampus on PND21 and 90. Due to analytical restrictions statistical comparisons of GFAP levels were limited to examining the effect of maternal PCB treatment per brain region per sex per time point. Calcineurin activity 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 maternal 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 microsomal EROD activity was highly induced following gestational and lactational PCB exposure; however, on PND90 EROD activity was unaffected by maternal PCB treatment in male offspring and significantly decreased in female offspring. The results of the present study indicate that gestational and lactational exposure to the commercial PCB mixture results in long-term alterations in a neuronal and glial cell markers in specific brain regions of rats. These marker proteins may be useful for determining the structure-activity relationships in PCB-induced developmental neurotoxicity.
Morse
D C
DC
Department of Toxicology, Agricultural University, Wageningen, The Netherlands. dcmorse@eohsi.rutgers.edu
Plug
A
A
Wesseling
W
W
van den Berg
K J
KJ
Brouwer
A
A
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D013956:Antithyroid Agents / Q000633:toxicity*; D001140:Aroclors / Q000633:toxicity*; D015415:Biomarkers; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D001933:Brain Stem / Q000187:drug effects / Q000201:enzymology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002531:Cerebellum / Q000187:drug effects / Q000201:enzymology; D020111:Chlorodiphenyl (54% Chlorine); D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis / Q000096:biosynthesis / Q000187:drug effects*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017208:Rats, Wistar; D012098:Reproduction / Q000187:drug effects; D016708:Synaptophysin / Q000096:biosynthesis / Q000187:drug effects*
D013956:Antithyroid Agents; D001140:Aroclors; D015415:Biomarkers; D005904:Glial Fibrillary Acidic Protein; D016708:Synaptophysin; D020111:Chlorodiphenyl (54% Chlorine); D019363:Cytochrome P-450 CYP1A1; D017871:Calcium-Calmodulin-Dependent Protein Kinases