Influence of a combination of two tetrachlorobiphenyl congeners (PCB 47; PCB 77) on thyroid status, choline acetyltransferase (ChAT) activity, and short- and long-term memory in 30-day-old Sprague-Dawley rats.

摘要

The important role of thyroid hormones in growth and development, maintenance of body temperature, digestion, cardiac function, and normal brain development can be disrupted by environmental contaminants like polychlorinated biphenyls (PCB). Polychlorinated biphenyls are environmental contaminants that are widespread, persistent, lipophilic, and bioaccumulate through food webs, concentrating in adipose tissue. Placental and lactational PCB exposure of offspring causes metabolic and endocrine disruptions including hypothyroxinemia, spatial learning and memory deficits, neurochemical and neurobehavioral alterations, and reproductive problems. Previous studies in our lab using the individual congeners PCB 47 (2,2',4,4'-tetrachlorobiphenyl, ortho-substituted) and PCB 77 (3,3',4,4'-tetrachlorobiphenyl, non-ortho-substituted) have demonstrated alterations in thyroid hormone levels, alterations in brain choline acetyltransferase (ChAT) activity, and spatial learning deficits. In the present study, pregnant Sprague-Dawley rats were fed a diet with or without a mixture of PCB 47/77 at 1.25 ppm, 12.5 ppm or 25.0 ppm (w/w). Rat pups were swum in the Morris water maze four times a day on days 21-29 in order for the animals to learn the position of a submerged fixed platform. A probe test was run on day 24 (30 min after last swim) for short-term memory, and on day 29 (24 h after the last swim) for long-term memory after removal of the platform. Time spent in the quadrant previously containing the platform was recorded. Rats were decapitated on day 30, serum collected and frozen at -20 degrees. ChAT activity was measured radiometrically in basal forebrain and hippocampus. All PCB-treated animals experienced a depression in both triiodothyronine (T3) and thyroxine (T4). The present study found that all doses of PCB depressed ChAT activity in hippocampus with no significant alteration in the basal forebrain. In PCB-treated animals, short-term memory showed a trend toward improvement and long-term memory toward depression, but these trends were not significant. The consequences likely stem from endocrine disruption, especially with regard to the thyroid.