title: Role of Rho-mediated ROCK-Semaphorin3A signaling pathway in the pathogenesis of Parkinson's disease in a mouse model.
abstract: OBJECTIVE
  The present study aims to elucidate the role of Rho-mediated ROCK-Semaphorin3A signaling pathway in the pathogenesis of Parkinson's disease (PD) in a mouse model.
  
  
  METHODS
  One-hundred twelve eight-week male C57BL/6 mice were selected. The mouse model of PD was constructed by intraperitoneal injection of MPTP. All mice were divided into four groups (28 mice in each group): Blank group, Model group, Rho knockout (Rho+/-) group and ROCK knockout (ROCK+/-) group. Changes of behavior of the mice were studied through automatic moving test and rotarod test. Immunohistochemistry (IHC) was used to detect the expressions of TH, CD11b and GFAP. High performance liquid chromatograph (HPLC) was performed for detection of dopamine and its metabolic product. The mRNA and protein expressions of Rho, ROCK, Sema3A, PlexinA and NRP-1 were detected using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting.
  
  
  RESULTS
  Rho and ROCK knockout improved the damage caused by MPTP on the behavior of mice and protected dopaminergic neurons from injury, along with the increases of dopamine and its metabolic product. The mRNA and protein expressions of Rho, ROCK, Sema3A, PlexinA and NRP-1 were increased in PD mice in the Model group compared with those in the Blank group. Compared to the Model group, the mRNA and protein expressions of Rho, ROCK, Sema3A, PlexinA and NRP-1 were reduced in the Rho+/- and ROCK+/- groups.
  
  
  CONCLUSIONS
  These findings indicate that Rho and ROCK knockout may improve the behavior of mice and prevent MPTP-induced dopaminergic neurons damage by regulating Sema3A, PlexinA and NRP-1 in a mouse model of PD.
authors: Department of Neurological Rehabilitation, The 181st Central Hospital of PLA, Guilin 541002, PR China.
authors: Li
authors: L
authors: Qi
authors: Department of Neurological Rehabilitation, The 181st Central Hospital of PLA, Guilin 541002, PR China.
authors: Yong-Gang
authors: YG
authors: Tang
authors: Department of Neurological Rehabilitation, The 181st Central Hospital of PLA, Guilin 541002, PR China.
authors: Lin
authors: L
authors: Wang
authors: Department of Neurological Rehabilitation, The 181st Central Hospital of PLA, Guilin 541002, PR China.
authors: Wei
authors: W
authors: He
authors: Department of Neurological Rehabilitation, The 181st Central Hospital of PLA, Guilin 541002, PR China.
authors: Hong-Hua
authors: HH
authors: Pan
authors: Department of Neurological Rehabilitation, The 181st Central Hospital of PLA, Guilin 541002, PR China. Electronic address: nie_rr@yeah.net.
authors: Rong-Rong
authors: RR
authors: Nie
authors: Department of Neurological Rehabilitation, The 181st Central Hospital of PLA, Guilin 541002, PR China.
authors: Yan
authors: Y
authors: Can
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000378:metabolism / Q000473:pathology; D059290:Dopaminergic Neurons / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D020267:MPTP Poisoning / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008636:Mesencephalon / Q000378:metabolism / Q000473:pathology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000066829:Neuroprotection / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D040121:Semaphorin-3A / Q000378:metabolism*; D015398:Signal Transduction; D054460:rho-Associated Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; C488217:Sema3a protein, mouse; D040121:Semaphorin-3A; D054460:rho-Associated Kinases
keywords: Parkinson's disease; ROCK; Rho; Semaphorin3A