HOMEPRODUCTSSERVICESCOMPANYCONTACTFAQResearchDictionaryPharmaMobileSign Up FREE or Login

A multitarget basal ganglia dopaminergic and GABAergic transplantation strategy enhances behavioural recovery in parkinsonian rats.

Abstract
The current transplantation paradigm for Parkinson's disease that places foetal dopaminergic cells in the striatum neither normalizes neuronal activity in basal ganglia structures such as the substantia nigra (SN) and subthalamic nucleus (STN) nor leads to complete functional recovery. It was hypothesized that restoration of parkinsonian deficits requires inhibition of the pathological overactivity of the STN and SN in addition to restoration of dopaminergic activity in the striatum. To achieve inhibition, a multitargeted basal ganglia transplantation strategy using GABAergic cells derived from either foetal striatal primordia (FSP) cells or human neural precursor cells (hNPCs) expanded in suspension bioreactors was investigated. In hemiparkinsonian rats, transplantation of foetal rat dopaminergic cells in the striatum in conjunction with GABAergic grafts in the STN and/or SN promoted significant improvement in forelimb akinesia and motor function compared to transplantation of intrastriatal dopaminergic grafts alone or in conjunction with undifferentiated hNPCs. In culture, FSP cells exhibited neuronal electrophysiological properties. However, recordings from GABAergic hNPCs revealed limited ionic conductances and an inability to fire action potentials. Despite this, they were almost as efficacious as FSP cells in inducing functional recovery following transplantation, suggesting that such recovery may have been mediated by secretion of GABA rather than by functional integration into the host. Thus, restoration of dopaminergic activity to the striatum in concert with inhibition of the STN and SN by GABAergic grafts may be beneficial for improving clinical outcomes in patients with Parkinson's disease and potential clinical application of this strategy may be enhanced by the use of differentiated hNPCs.
AuthorsK Mukhida, M Hong, G B Miles, T Phillips, B A Baghbaderani, M McLeod, N Kobayashi, A Sen, L A Behie, R M Brownstone, I Mendez
JournalBrain : a journal of neurology (Brain) Vol. 131 Issue Pt 8 Pg. 2106-26 (Aug 2008) ISSN: 1460-2156 [Electronic] England
PMID18669492 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • gamma-Aminobutyric Acid
  • Dopamine
Topics
  • Animals
  • Basal Ganglia (metabolism)
  • Dopamine (metabolism)
  • Female
  • Fetal Stem Cells (transplantation)
  • Humans
  • Immunohistochemistry
  • Microscopy, Confocal
  • Models, Animal
  • Neurons (transplantation)
  • Neuropsychological Tests
  • Parkinsonian Disorders (metabolism, surgery)
  • Random Allocation
  • Rats
  • Rats, Wistar
  • Substantia Nigra
  • Subthalamic Nucleus
  • Treatment Outcome
  • gamma-Aminobutyric Acid (metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!


Choose Username:
Email:
Password:
Verify Password: