An organotypic culture model to study nigro-striatal degeneration

J Neurosci Methods. 2010 May 15;188(2):205-12. doi: 10.1016/j.jneumeth.2010.02.008. Epub 2010 Feb 11.

Abstract

Functional and reliable in vitro models of Parkinson's disease (PD) are valuable for studying mechanisms of dopaminergic degeneration before proceeding to animal testing. At present, all in vitro models involve substitute cell types and thus their direct relevance to PD is questionable. Here, we describe an organotypic culture model which conserves the 3D architecture of the nigro-striatal pathway, together with the subventricular zone and cerebral cortex, and recapitulates a specific pattern of dopaminergic degeneration which is the principal hallmark of PD. The organotypic culture is kept in vitro for up to 12 days and dopaminergic degeneration is induced by the simple cutting of dopaminergic fibers. This organotypic model represents a rapid and useful method (30 min/pup for preparation and up to 12 days of cultivation) to investigate in vitro the mechanisms underlying neuronal death and protection, as well as neurogenesis and repair after nigro-striatal neurodegeneration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Antiparkinson Agents / pharmacology
  • Axotomy / methods
  • Cell Proliferation / drug effects
  • Corpus Striatum / metabolism
  • Corpus Striatum / pathology
  • Corpus Striatum / physiopathology*
  • Dopamine / metabolism
  • Microdissection / methods
  • Nerve Degeneration / metabolism
  • Nerve Degeneration / pathology
  • Nerve Degeneration / physiopathology*
  • Nerve Growth Factors / pharmacology
  • Nerve Regeneration / drug effects
  • Nerve Regeneration / physiology
  • Neural Pathways / metabolism
  • Neural Pathways / pathology
  • Neural Pathways / physiopathology
  • Neurogenesis / drug effects
  • Neurogenesis / physiology
  • Organ Culture Techniques / methods
  • Parkinson Disease / drug therapy
  • Parkinson Disease / pathology
  • Parkinson Disease / physiopathology
  • Rats
  • Rats, Sprague-Dawley
  • Stem Cells / cytology
  • Stem Cells / drug effects
  • Stem Cells / metabolism
  • Substantia Nigra / metabolism
  • Substantia Nigra / pathology
  • Substantia Nigra / physiopathology*
  • Time Factors

Substances

  • Antiparkinson Agents
  • Nerve Growth Factors
  • Dopamine