Exposure to polybrominated diphenyl ethers 203 and 206 during the neonatal brain growth spurt affects proteins important for normal neurodevelopment in mice.
The period of rapid brain growth and development (BGS) is postnatal in mice and rats, spanning the first 3-4 weeks of life, reaching its peak around postnatal day 10, whereas in humans, the BGS is perinatal. CaMKII, GAP-43, synaptophysin, and tau play important roles during the BGS. One class of flame retardants, polybrominated diphenyl ethers (PBDEs), is present and increasing in the environment and in human milk. The only congener still in use, decabrominated diphenyl ether (PBDE 209), is thought to be debrominated into lower brominated congeners. In the present study, nona- and octabrominated PBDEs were examined. Neonatal mice were exposed to 21 mumol PBDE 203 or 206/kg bodyweight on postnatal day 10, and different brain regions were analyzed for CaMKII, GAP-43, synaptophysin, and tau, 24 h after exposure. The protein analysis showed that CaMKII and synaptophysin increased significantly in the hippocampus, but not in the cerebral cortex, after neonatal exposure to PBDE 203 or 206. Furthermore, there were no significant changes in the levels of GAP-43 and tau in the cerebral cortex or hippocampus after neonatal exposure to PBDE 203 or 206. This shows that PBDE 203 and 206 affect important proteins involved in normal maturation of the brain and strengthens our findings that highly brominated PBDEs cause developmental neurotoxicity. In addition, the increases in CaMKII and synaptophysin are the same changes seen after neonatal PBDE 209 exposure; supporting the suggestion that PBDE 209 must be metabolized, likely debrominated into lower brominated PBDEs, to exert its neurotoxic effects.
Viberg
Henrik
H
Department of Environmental Toxicology, Uppsala University, Norbyvägen 18A, S-752 36 Uppsala, Sweden. henrik.viberg@ebc.uu.se
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D005260:Female; D019922:GAP-43 Protein / Q000378:metabolism; D055768:Halogenated Diphenyl Ethers / Q000008:administration & dosage / Q000633:toxicity*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D011247:Pregnancy; D016708:Synaptophysin / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism
D019922:GAP-43 Protein; D055768:Halogenated Diphenyl Ethers; D016708:Synaptophysin; D016875:tau Proteins; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2