Intrastriatal transplantation of GDNF-engineered BMSCs and its neuroprotection in lactacystin-induced Parkinsonian rat model

Neurochem Res. 2010 Mar;35(3):495-502. doi: 10.1007/s11064-009-0086-6. Epub 2009 Nov 6.

Abstract

The potential value of glial cell line-derived neurotrophic factor (GDNF) in treating Parkinson's disease (PD) remains controversial. In order to evaluate the therapeutic effect of GDNF-engineered bone marrow stromal cells (BMSCs) in parkinsonian rat model, GDNF-BMSCs and LacZ-BMSCs were transplanted into striatum and followed by Lactacystin lesioning at median forebrain bundles 1 week later. We observed that the intrastriatal transplantation of GDNF-BMSCs could significantly rescue the dopaminergic neurons from lactacystin-induced neurotoxicity with regard to behavioral recovery, tyrosine hydroxylase level in nigra and striatum, and striatal dopamine level. We interpret the outcomes that intrastriatal transplantation of GDNF-BMSCs might be beneficial in the treatment of PD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / analogs & derivatives*
  • Acetylcysteine / antagonists & inhibitors
  • Acetylcysteine / toxicity
  • Animals
  • Antimetabolites
  • Apomorphine
  • Behavior, Animal / drug effects
  • Blotting, Western
  • Bone Marrow Transplantation / physiology*
  • Bromodeoxyuridine
  • Cysteine Proteinase Inhibitors / toxicity*
  • Dopamine / metabolism
  • Dopamine Agonists
  • Glial Cell Line-Derived Neurotrophic Factor / genetics
  • Glial Cell Line-Derived Neurotrophic Factor / physiology*
  • Immunohistochemistry
  • Neostriatum / drug effects
  • Neostriatum / metabolism
  • Neostriatum / physiology*
  • Parkinson Disease, Secondary / chemically induced*
  • Parkinson Disease, Secondary / prevention & control*
  • Parkinson Disease, Secondary / psychology
  • Rats
  • Rats, Sprague-Dawley
  • Stereotyped Behavior / drug effects
  • Tissue Engineering
  • Tyrosine 3-Monooxygenase / metabolism

Substances

  • Antimetabolites
  • Cysteine Proteinase Inhibitors
  • Dopamine Agonists
  • Glial Cell Line-Derived Neurotrophic Factor
  • lactacystin
  • Tyrosine 3-Monooxygenase
  • Bromodeoxyuridine
  • Apomorphine
  • Dopamine
  • Acetylcysteine