title: TLR4 signaling mediates AP-1 activation in an MPTP-induced mouse model of Parkinson's disease.
abstract: OBJECTIVE
  To evaluate the effects of Toll-like receptor 4 (TLR4) signaling on the activation of the transcription factor activator protein-1 (AP-1) in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of Parkinson's disease (PD).
  
  
  METHODS
  The following groups were evaluated: normal saline (NS)-treated WT mice, NS-treated TLR4-knockout (KO) mice, MPTP-treated WT mice, and MPTP-treated TLR4-KO mice. After establishing the mouse model, behavioral changes were evaluated. AP-1 expression was detected by RT-PCR, Western blotting, immunohistochemistry and immunofluorescence staining.
  
  
  RESULTS
  Compared to MPTP-treated WT mice, significantly reduced dyskinesia was observed in MPTP-treated TLR4-KO mice. AP-1 mRNA and protein levels were significantly up-regulated in the substantia nigras (SNs) of MPTP-treated WT mice relative to NS-treated mice (P<0.01); these levels were significantly reduced in MPTP-treated TLR4-KO mice relative to MPTP-treated WT mice (P<0.01). Immunohistochemical staining demonstrated that AP-1 was distributed throughout the SN in MPTP-treated mice, and immunofluorescence further showed that AP-1 was expressed in TH-positive neuronal cells and GFAP-positive astrocytes. In addition, immunofluorescence revealed that AP-1 expression was lower in TH-positive neurons and GFAP-positive astrocytes in the SNs of MPTP-treated TLR4-KO mice relative to MPTP-treated WT mice.
  
  
  CONCLUSIONS
  The TLR4 pathway may play an important role in regulating AP-1 activation.
authors.affiliation: School of Pharmacy, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Xu-Dong
authors.initials: XD
authors.lastname: Zhao
authors.affiliation: Department of Neurology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors.forename: Fa-Xiang
authors.initials: FX
authors.lastname: Wang
authors.affiliation: Department of Traditional Chinese Medicine, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Wen-Fu
authors.initials: WF
authors.lastname: Cao
authors.affiliation: School of Pharmacy, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Yong-Hong
authors.initials: YH
authors.lastname: Zhang
authors.affiliation: Department of Traditional Chinese Medicine, Chongqing Medical University, Chongqing 400016, China. Electronic address: liyancq8866@sina.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001522:Behavior, Animal; D004195:Disease Models, Animal; D008297:Male; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D018808:Transcription Factor AP-1; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
keywords: AP-1; MPTP; Parkinson's disease; TLR4