title: Mildronate as a regulator of protein expression in a rat model of Parkinson's disease.
abstract: BACKGROUND
  Mildronate (3-[2,2,2-trimethylhydrazinium] propionate dihydrate) traditionally is a well-known cardioprotective drug. However, our recent studies convincingly demonstrated its neuroprotective properties. The aim of the present study was to evaluate the influence of mildronate on the expression of proteins that are involved in the differentiation and survival of the nigrostriatal dopaminergic neurons in the rat model of Parkinson's disease (PD). The following biomarkers were used: heat shock protein 70 (Hsp70, a molecular chaperone), glial cell line-derived nerve growth factor (GDNF, a growth factor promoting neuronal differentiation, regeneration, and survival), and neural cell adhesion molecule (NCAM).
  
  
  METHODS
  PD was modeled by 6-hydroxydopamine (6-OHDA) unilateral intrastriatal injection in rats. Mildronate was administered at doses of 10, 20, and 50 mg/kg for 2 weeks intraperitoneally before 6-OHDA injection. Rat brains were dissected on day 28 after discontinuation of mildronate injections. The expression of biomarkers was assessed immunohistochemically and by western blot assay.
  
  
  RESULTS
  6-OHDA decreased the expression of Hsp70 and GDNF in the lesioned striatum and substantia nigra, whereas in mildronate-pretreated (20 and 50 mg/kg) rats, the expression of Hsp70 and GDNF was close to the control group values. NCAM expression also was decreased by 6-OHDA in the striatum and it was totally protected by mildronate at a dose of 50 mg/kg. In contrast, in the substantia nigra, 6-OHDA increased the expression of NCAM, while mildronate pretreatment (20 and 50 mg/kg) reversed the 6-OHDA-induced overexpression of NCAM close to the control values.
  
  
  CONCLUSIONS
  The obtained data showed that mildronate was capable to regulate the expression of proteins that play a role in the homeostasis of neuro-glial processes.
authors.affiliation: Department of Pathology, University of Latvia, Riga. Latvia. sergisajevs@inbox.lv
authors.forename: Sergejs
authors.initials: S
authors.lastname: Isajevs
authors.forename: Darja
authors.initials: D
authors.lastname: Isajeva
authors.forename: Ulrika
authors.initials: U
authors.lastname: Beitnere
authors.forename: Baiba
authors.initials: B
authors.lastname: Jansone
authors.forename: Ivars
authors.initials: I
authors.lastname: Kalvinsh
authors.forename: Vija
authors.initials: V
authors.lastname: Klusa
mesh_terms: D000818:Animals; D002317:Cardiovascular Agents / Q000008:administration & dosage*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D018840:HSP70 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D008297:Male; D008763:Methylhydrazines / Q000008:administration & dosage*; D019006:Neural Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D016627:Oxidopamine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010302:Parkinson Disease, Secondary / Q000188:drug therapy* / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism
chemical_list: D002317:Cardiovascular Agents; D051100:Glial Cell Line-Derived Neurotrophic Factor; D018840:HSP70 Heat-Shock Proteins; D008763:Methylhydrazines; D019006:Neural Cell Adhesion Molecules; D018696:Neuroprotective Agents; C050147:3-(2,2,2-trimethylhydrazine)propionate; D016627:Oxidopamine