Age-dependent effects of Aroclor 1254(R) on calcium uptake by subcellular organelles in selected brain regions of rats

Earlier reports from our laboratory have indicated that polychlorinated bip henyls (PCBs) affect signal transduction mechanisms in brain, including Ca2 + homeostasis, phosphoinositol hydrolysis, and protein kinase C (PKC) trans location in mature neurons and adult brain homogenate preparations. Present studies were designed to investigate whether there were any brain region-, gender-, or age-dependent effects of PCBs on Ca-45(2+)-uptake by two subce llular organelles, microsomes and mitochondria. We have studied in vitro ef fects of a widely studied commercial PCB mixture, Aroclor 1254(R), on Ca-45 (2+)-uptake by microsomes and mitochondria in cerebellum, frontal cortex an d hippocampus of postnatal day (PND) 7, 21, and 90-120 (adult) male and fem ale Long-Evans (LE)-rats. In general, microsomal and mitochondrial Ca-45(2)-uptake in selected brain regions increased with age; PND 7 < PND 21 <less than or equal to> adults. Among three brain regions, hippocampus had relat ively lower microsomal Ca-45(2+)-uptake than cerebellum and frontal cortex throughout the development. Mitochondrial Ca-45(2+)-uptake was comparable i n three brain regions of PND 7 and adult animals, but in PND 21 rats, the c erebellum had much higher activity than frontal cortex and hippocampus. No gender-related differences were seen in Ca-45(2+)-uptake by either microsom es or mitochondria in selected brain regions throughout development. Inhibi tion of Ca-45(2+)-uptake by Aroclor 1254 in a concentration-dependent manne r was observed throughout the study. However, the degree of inhibition of m icrosomal Ca-45(2+)-uptake in these brain regions by Aroclor 1254 increased with age, PND 7 < PND 21 <less than or equal to> adults (IC(50)s = 21-34, 8-20 and 10-14 muM, respectively). Brain region-specific differential sensi tivity to Aroclor 1254 on the inhibition of microsomal Ca-45(2+)-uptake was not seen in PND 7 and adult animals but in PND 21 rats, hippocampus was mo re sensitive than the other selected brain regions. There were no age-, gen der- or brain region-specific differential effects of Aroclor 1254 on mitoc hondrial Ca-45(2+)-uptake. These results indicate that a commercial PCB mix ture. Aroclor 1254, inhibited Ca-45(2+)-uptake by both microsomes and mitoc hondria uniformly in selected brain regions of males and females during dev elopment. However, the inhibition of microsomal Ca-45(2+)-uptake by Aroclor 1254 increased with age. The age- and gender-related differential sensitiv ity to Aroclor 1254 may be attributed to the changes in calcium homeostasis in various brain regions during development. (C) 2156 Elsevier Science Ire land Ltd. All rights reserved.