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Perinatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin suppresses contextual fear conditioning-accompanied activation of cyclic AMP response element-binding protein in the hippocampal CA1 region of male rats
Authors:Tetsuo Mitsui  Nobuhiro Sugiyama  Shuichiro Maeda  Chiharu Tohyama  Jun Arita
Affiliation:1. Department of Physiology, Interdisciplinary Graduate School of Medicine and Engineering, The University of Yamanashi, Yamanashi 409-3898, Japan;2. Department of Biochemistry, Interdisciplinary Graduate School of Medicine and Engineering, The University of Yamanashi, Yamanashi 409-3898, Japan;3. Division of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo Tokyo 113-0033, Japan
Abstract:
We investigated the effect of in utero and lactational exposures to dioxin on adult offspring with contextual fear conditioning, a sex- and hippocampus-dependent learning paradigm; and we measured the conditioning-accompanied activation of cyclic AMP response element-binding protein (CREB) in the hippocampal CA1 region. Pregnant rats were treated with a low dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on gestation day 15. TCDD treatment decreased freezing time in conditioning tests of adult male offspring but not of female offspring. A similar, male-specific decrease was observed in the percentage of phosphorylated CREB-immunoreactive neurons in the CA1 region following conditioning in TCDD-treated rats. These results suggest that perinatal TCDD exposure impairs hippocampus-dependent learning in male offspring by suppressing CREB activation.
Keywords:Dioxin   Contextual fear conditioning   Cyclic AMP response element-binding protein (CREB)   Sex difference   Hippocampus
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