title: Effects of simvastatin on the expression of inducible nitric oxide synthase and brain-derived neurotrophic factor in a lipopolysaccharide-induced rat model of Parkinson disease.
abstract: OBJECTIVE
  To investigate the effects of simvastatin on the expression of inducible nitric oxide synthase (iNOS) and brain-derived neurotrophic factor (BDNF) in the substantia nigra in a lipopolysaccharide (LPS)-induced rat model of Parkinson disease (PD), and to study the mechanisms underlying the neuroprotective effects of simvastatin in PD.
  
  
  METHODS
  The LPS-PD model was established by injection of LPS (5 mg/mL, 2.0 μL) into the right substantia nigra compacta (SNC). Rats in the sham-operated group received saline. The simvastatin treatment group was intraperitoneally administered simvastatin (5 mg/kg, 2.0 μL) at 1 h before, and daily for 14 days after surgery, while the sham-operated and LPS-model groups received saline. Iba-1-positive cells and tyrosine hydroxylase (TH), as well as iNOS and BDNF in the SNC were detected by immunohistochemistry and Western blotting, respectively. The effect of simvastatin in the PD model was also examined in behavioral tests.
  
  
  RESULTS
  The LPS-model group exhibited typical animal PD behaviors. Compared with the control group, the LPS-model group exhibited a decreased number of DA neurons (p < 0.01) in the SNC, as well as increases in the Iba-1-positive cell number and iNOS expression (p < 0.05), while BDNF expression was downregulated (p < 0.01). These effects were inhibited by simvastatin treatment (p < 0.05).
  
  
  CONCLUSIONS
  Simvastatin mediates a protective effect on dopaminergic neurons in the SNC in the LPS-PD model, possibly by promoting neuronal repair and regeneration, and by inhibiting oxidative stress, thus improving substantia nigra function.
authors.affiliation: a Department of Neurology, Xiangya Hospital , Central South University , Changsha , China ;|b Department of Neurology , Affiliated Hospital of Hainan Medical College , Haikou , China ;
authors.forename: Wang
authors.initials: W
authors.lastname: Tan
authors.affiliation: c Department of Neurology, Union Hospital, Tongji Medical College , Huazhong University of Science and Technology , Wuhan , China.
authors.forename: Cao
authors.initials: C
authors.lastname: Xue-bin
authors.affiliation: b Department of Neurology , Affiliated Hospital of Hainan Medical College , Haikou , China ;
authors.forename: Zhang
authors.initials: Z
authors.lastname: Tian
authors.affiliation: b Department of Neurology , Affiliated Hospital of Hainan Medical College , Haikou , China ;
authors.forename: Chen
authors.initials: C
authors.lastname: Xiao-wu
authors.affiliation: c Department of Neurology, Union Hospital, Tongji Medical College , Huazhong University of Science and Technology , Wuhan , China.
authors.forename: Huang
authors.initials: H
authors.lastname: Pei-pei
authors.affiliation: b Department of Neurology , Affiliated Hospital of Hainan Medical College , Haikou , China ;
authors.forename: Chen
authors.initials: C
authors.lastname: Zhi-bin
authors.affiliation: a Department of Neurology, Xiangya Hospital , Central South University , Changsha , China ;
authors.forename: Tang
authors.initials: T
authors.lastname: Bei-sha
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000378:metabolism*; D065842:Pars Compacta / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019821:Simvastatin / Q000494:pharmacology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D008070:Lipopolysaccharides; D018696:Neuroprotective Agents; D019821:Simvastatin; D052247:Nitric Oxide Synthase Type II; D014446:Tyrosine 3-Monooxygenase
keywords: BDNF; Parkinson disease; Simvastatin; iNOS