| Autor: |
Chen H; Department of Molecular Biosciences, University of California, Davis, CA 95616, USA., Carty RK; Department of Molecular Biosciences, University of California, Davis, CA 95616, USA., Bautista AC; Department of Molecular Biosciences, University of California, Davis, CA 95616, USA., Hayakawa KA; Department of Molecular Biosciences, University of California, Davis, CA 95616, USA., Lein PJ; Department of Molecular Biosciences, University of California, Davis, CA 95616, USA. |
| Abstrakt: |
We previously demonstrated that polybrominated diphenyl ethers (PBDEs) inhibit the growth of axons in primary rat hippocampal neurons. Here, we test the hypothesis that PBDE effects on axonal morphogenesis are mediated by thyroid hormone and/or reactive oxygen species (ROS)-dependent mechanisms. Axonal growth and ROS were quantified in primary neuronal-glial co-cultures dissociated from neonatal rat hippocampi exposed to nM concentrations of BDE-47 or BDE-49 in the absence or presence of triiodothyronine (T3; 3-30 nM), N-acetyl-cysteine (NAC; 100 µM), or α-tocopherol (100 µM). Co-exposure to T3 or either antioxidant prevented inhibition of axonal growth in hippocampal cultures exposed to BDE-47 or BDE-49. T3 supplementation in cultures not exposed to PBDEs did not alter axonal growth. T3 did, however, prevent PBDE-induced ROS generation and alterations in mitochondrial metabolism. Collectively, our data indicate that PBDEs inhibit axonal growth via ROS-dependent mechanisms, and that T3 protects axonal growth by inhibiting PBDE-induced ROS. These observations suggest that co-exposure to endocrine disruptors that decrease TH signaling in the brain may increase vulnerability to the adverse effects of developmental PBDE exposure on axonal morphogenesis. |
