title: Involvement of mGlu5 receptor in 3-nitropropionic acid-induced oxidative stress in rat striatum.
abstract: OBJECTIVE
  The excitotoxin 3-nitropropionic acid (3-NP) induces a suitable experimental model of Huntington's disease (HD). This compound induces neurodegeneration via glutamatergic activation and oxidative stress, suggesting that the metabotropic glutamate receptor blockage and free radical scavenging are potential therapeutic targets in HD. In this study, we evaluated the role of 3-[(2-methyl-1,3-thiazol-4-yl) ethynyl]-pyridine (MTEP), a selective mGlu5 receptor antagonist, in a 3-NP model of HD.
  
  
  METHODS
  We administered 3-NP (20 mg/kg, intraperitoneal) to rats for 4 days. MTEP at doses of 2·5 and 5 mg/kg was administered 30 min before 3-NP. Behavioral tests and biochemical experiments were performed to assess the effects of 3-NP and the ability of MTEP to ameliorate these changes.
  
  
  RESULTS
  3-NP administration induced body weight loss, decreased locomotor activity, and inhibition of succinate dehydrogenase and Na(+)-K(+) adenosine triphosphate (ATP)ase activities in rat striatum. We also observed increases in reactive species (RS) levels and glutathione reductase activity, decreased non-protein thiol levels, and an inhibition of glutathione peroxidase activity in the striatum of rats treated with 3-NP. Notably, all of these effects were attenuated by MTEP treatment.
  
  
  CONCLUSIONS
  Our results demonstrate the neuroprotective effect of MTEP and reinforce the involvement of mGluR5 in 3-NP-induced oxidative stress in rat striatum.
authors.forename: Leandro C
authors.initials: LC
authors.lastname: Souza
authors.forename: Ethel A
authors.initials: EA
authors.lastname: Wilhelm
authors.forename: Cristiani F
authors.initials: CF
authors.lastname: Bortolatto
authors.forename: Cristina W
authors.initials: CW
authors.lastname: Nogueira
authors.forename: Silvana P
authors.initials: SP
authors.lastname: Boeira
authors.forename: Cristiano R
authors.initials: CR
authors.lastname: Jesse
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D006816:Huntington Disease / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009574:Nitro Compounds; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D011422:Propionates; D011725:Pyridines / Q000494:pharmacology*; D017208:Rats, Wistar; D064529:Receptor, Metabotropic Glutamate 5 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013385:Succinate Dehydrogenase / Q000378:metabolism; D013844:Thiazoles / Q000494:pharmacology*; D015431:Weight Loss / Q000187:drug effects / Q000502:physiology
chemical_list: C472365:3-((2-methyl-1,3-thiazol-4-yl)ethynyl)pyridine; C578937:Grm5 protein, rat; D018696:Neuroprotective Agents; D009574:Nitro Compounds; D011422:Propionates; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5; D013844:Thiazoles; D005979:Glutathione Peroxidase; D013385:Succinate Dehydrogenase; D005980:Glutathione Reductase; D000254:Sodium-Potassium-Exchanging ATPase; C015392:3-nitropropionic acid
keywords: 3-nitropropionic acid,; Glutamatergic activation,; Huntington’s disease,; MTEP,; Metabotropic glutamate receptor,; Oxidative stress