title: Involvement of TLR4 in diazinon-induced neurotoxicity in mice.
abstract: Our laboratory recently reported that Toll-like receptor (TLR) 4 may play a role in the neurotoxic effects in mice exposed to the environmental toxic chemical toluene. To investigate the role of TLR4 in hippocampal neurotrophin expression, C3H/HeN (TLR4 intact) and C3H/HeJ (TLR4 defective) male adult mice were administered diazinon (0, 0.05, 0.5 or 5 mg/kg) intraperitoneally once a week for three weeks. Twenty-four hours after the final diazinon injection, the hippocampus was collected from each mouse to detect mRNA expression of neurotrophins (nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF)) by the real-time RT-PCR method. There was no difference between groups in neurotrophin expression in the C3H/HeN mice. However, the expression of NGF and BDNF mRNAs was suppressed significantly in the diazinon-injected C3H/HeJ mice compared with their control group. We also found an increased tendency of proinflammatory chemokine CCL3 mRNA and a marked increase in the proapoptotic gene Bax mRNA in the diazinon-injected C3H/HeJ mice. Our findings indicate that diazinon injection affects neurotrophin expression in the hippocampus in TLR4-defective mice but not in TLR4 intact mice. These results suggest that a defective TLR4 signaling pathway in the mouse hippocampus can be easily affected by diazinon administration.
authors.affiliation: Center for Environmental Health Sciences, National Institute for Environmental Studies, Onogawa, Tsukuba, Ibaraki 305-8506, Japan.
authors.forename: Tin-Tin
authors.initials: TT
authors.lastname: Win-Shwe
authors.forename: Daisuke
authors.initials: D
authors.lastname: Nakajima
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Fujimaki
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000032:analysis; D054405:Chemokine CCL3 / Q000235:genetics; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D003976:Diazinon / Q000008:administration & dosage / Q000494:pharmacology*; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009414:Nerve Growth Factors / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis / Q000502:physiology*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D054405:Chemokine CCL3; D002800:Cholinesterase Inhibitors; D009414:Nerve Growth Factors; D012333:RNA, Messenger; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D003976:Diazinon