Proteomic identification of biomarkers in the cerebrospinal fluid in a rat model of nigrostriatal dopaminergic degeneration

J Neurosci Res. 2007 Dec;85(16):3607-18. doi: 10.1002/jnr.21452.

Abstract

We have performed proteomic analysis in the cerebrospinal fluid in an animal model of Parkinson's disease induced by axotomy of the medial forebrain bundle. In this model, the degeneration of dopaminergic neurons was completed in 14 days, with a loss of about 50% dopaminergic neurons in the substantia nigra and a loss of more than 80% dopamine terminals in the striatum, with a similar diminution of dopamine levels in both structures. Proteins were separated by 2D electrophoresis and identified by matrix-assisted laser desorption-ionization time-of-flight (MALDI-TOF). We found significant increases of haptoglobin and transthyretin along with a decrease of Apo E concentrations in the cerebrospinal fluid of axotomized animals. Changes for haptoglobin and transthyretin were further confirmed in cerebrospinal fluid and plasma by Western blotting. These results suggest that monitoring plasma levels of these signals appears to be a promising biological marker of neuronal degeneration of the nigrostriatal dopaminergic system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apolipoproteins E / analysis
  • Apolipoproteins E / cerebrospinal fluid
  • Axotomy
  • Biomarkers / analysis
  • Biomarkers / cerebrospinal fluid
  • Cerebrospinal Fluid / chemistry
  • Corpus Striatum / metabolism*
  • Corpus Striatum / physiopathology
  • Disease Models, Animal
  • Dopamine / metabolism
  • Down-Regulation / physiology
  • Electrophoresis, Gel, Two-Dimensional / methods
  • Haptoglobins / analysis
  • Haptoglobins / cerebrospinal fluid
  • Nerve Degeneration / cerebrospinal fluid*
  • Nerve Degeneration / diagnosis
  • Nerve Degeneration / physiopathology
  • Neural Pathways / injuries
  • Neural Pathways / metabolism*
  • Neural Pathways / physiopathology
  • Parkinsonian Disorders / cerebrospinal fluid*
  • Parkinsonian Disorders / diagnosis
  • Parkinsonian Disorders / physiopathology
  • Prealbumin / analysis
  • Prealbumin / cerebrospinal fluid
  • Predictive Value of Tests
  • Proteomics / methods*
  • Rats
  • Rats, Wistar
  • Sensitivity and Specificity
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / methods
  • Substantia Nigra / injuries
  • Substantia Nigra / metabolism*
  • Substantia Nigra / physiopathology
  • Up-Regulation / physiology

Substances

  • Apolipoproteins E
  • Biomarkers
  • Haptoglobins
  • Prealbumin
  • Dopamine