Significant up-regulation of nestin protein in the neostriatum of MPTP-treated mice. Are the striatal astrocytes regionally activated after systemic MPTP administration?

Brain Res. 2002 Jan 18;925(1):9-17. doi: 10.1016/s0006-8993(01)03253-x.

Abstract

We are interested in the possible role of central glial cells in pathogenesis of Parkinson's disease of mammals. Parkinsonism model was induced by systemic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration, and the reactive glial cells were examined by immunocytochemical visualization of nestin protein in the brains and spinal cords of C57 mice. Abundant nestin-like immunoreactivity was predominately found in the caudate putamen of MPTP-treated mice and about 481-fold of nestin-like immunoreactive cells increased compared with that of control animals, indicating that significant up-regulation of nestin protein occurred in these regions. Majority of nestin-like immunoreactive cells characterized with astrocytic profiles of multiple, radical and hypotrophic processes, and showed a distribution and dynamic patterns similar to that of glial fibrillary acid protein (GFAP)-immunoreactive cells in the caudate putamen. Double immunofluorescence confirmed that 100% of nestin-like immunoreactive cells exhibited GFAP-immunoreactivity while nestin/GFAP double-labeled cells constituted about 84% of total GFAP-immunoreactive cells in the caudate putamen, indicating these nestin-like immunoreactive cells belong to a reactive population of the astrocytes. On the other hand, no obvious changes of nestin- or GFAP-like immunoreactivities were detected in the globus pallidus, the substantia nigra and the ventral tegmental area after MPTP-treatment. The results have provided morphological evidence for the regional activation of astrocytic glial cells following systemic MPTP administration, suggesting that a large population of reactive striatal astrocytes might play an important role in initial pathogenesis or acute stage of Parkinson's disease in mammals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / pharmacology
  • Animals
  • Astrocytes / chemistry
  • Astrocytes / metabolism*
  • Dopamine Agents / pharmacology
  • Glial Fibrillary Acidic Protein / analysis
  • Intermediate Filament Proteins / analysis
  • Intermediate Filament Proteins / metabolism*
  • MPTP Poisoning / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neostriatum / cytology
  • Neostriatum / metabolism*
  • Nerve Tissue Proteins*
  • Nestin
  • Spinal Cord / cytology
  • Spinal Cord / metabolism

Substances

  • Dopamine Agents
  • Glial Fibrillary Acidic Protein
  • Intermediate Filament Proteins
  • Nerve Tissue Proteins
  • Nes protein, mouse
  • Nestin
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine