The Neurotoxicology Of Decabrominated Diphenyl Ether

Polybrominated diphenyl ethers (PBDEs) is one of the flame-retardant additives, which is largely used in all parts of our lives. Its wide use has caused persistently environmental contamination. There are 209 congeners of PBDEs, and the penta- and octa-brominated diphenyl ethers have been banned by European Union and America for their toxic effects. But the decabrominated diphenyl ether (PBDE209), as the primary commercial product of PBDEs, still persistent and widely use. Previous studies indicated that many organs are targets of PBDEs, especially the central nervous system (CNS). Hippocampus is a region related to learning and memory. Impairing hippocampus may be one of the pathways that PBDEs impair the CNS. In this study, we investigated in depth the effects of PBDE 209 on the CNS, using behavioral and electrophysiological techniques, by morris water maze, field potential recording and patch clamp methods.1. The effects of PBDE209 on spatial learning and memory.Learning and memory is one of the most important functions of the CNS. There are many methods to study learning and memory. Morris water maze is one of the most frequently used methods, which is used to study and evaluate the spatial learning and memory of the rodents. In our study, we detected the effects of PBDE209 on the learning and memory of C57BL/6J mice through Morris water maze. The results showed PBDE209 could prolong the time and distance of mice finding the hide plate in the place navigation, and also changed the rate of distance and time between mice in target quadrant and all the quadrants in the spatial probe. Our founding indicated that PBDE209 could affect the learning process in the place navigation, and also affect the memory recall process and search strategy in the spatial probe. These confirm that PBDE209 can impair the spatial learning and memory of the CNS.2. The influence of PBDE 209 on synaptic plasticity in the rat dentate gyrus (DG) in vivo.The activity-dependent synaptic plasticity of hippocampus is regarded as the electrophysioloical substrate of learning and memory. We studied the effects of PBDE209 on synaptic plasticity in the DG in vivo, and discussed different effects of PBDE209 in the different developmental periods. The results demonstrated that PBDE 209 could impair the basic synaptic transmission, the paired-pulse reactions (PPR) and the long-term potentiation (LTP) of the field excitatory postsynaptic potential (fEPSP) slope and the population spike (PS) amplitude, and the lactation period is the most sensitive time of development towards PBDE 209. It was also found that PBDE 209 received from mother in early developmental periods play an important role to the toxic effects of PBDE 209 in whole range exposure.3. The effects of PBDEs on voltage-gated sodium channels (VGSCs) in rat primary cultured hippocampal neurons.VGSCs are responsible for both initiation and propagation of action potentials of the neurons in the hippocampus and throughout the central nervous system. Therefore, modulation of the functional properties of VGSCs would be expected to alter the activity and function of CNS neurons. We recorded TTX-sensitive voltage-gated sodium channels currents (I_Na) in rat primary cultured hippocampal neurons and studied the effects of PBDE 209 on I_Na and their kinetic properties, when the voltage-gated potassium channels and calcium channels were blocked. The results showed that PBDE 209 could irreversibly decrease I_Na in a concentration-dependent manner and the lowest assayed concentration was 0.1μM, PBDE 209 could shift the activation and inactivation of I_Na toward hyperpolarizing direction, prolong the time course of activation and fast inactivation, slow down the recovery from inactivation of I_Na, and decrease the fraction of activated sodium channels. These results suggested that PBDE 209 could modulate voltage-gated sodium channels (VGSCs), which may lead to change in electrical activity and contribute to worsen the neurotoxicological damage. Furthermore, ascorbic acid, as an antioxidant, was found capable of partially reversing those effects, which indicates that PBDE 209 might inhibit I_Na through peroxidation.