Longitudinal and parallel monitoring of neuroinflammation and neurodegeneration in a 6-hydroxydopamine rat model of Parkinson's disease

Synapse. 2012 Jul;66(7):573-83. doi: 10.1002/syn.21543. Epub 2012 Feb 15.

Abstract

As neuroinflammatory processes are involved in the pathogenesis of Parkinson's disease (PD), we achieved the longitudinal evaluation of them in parallel with the modifications of dopaminergic function at several time-points after 6-hydroxydopamine (6-OHDA) lesion in the rat mimicking an early stage of PD. After unilateral intrastriatal 6-OHDA administration, we quantified the temporal evolution of the 18 kDa translocator protein (TSPO), TH-immunoreactivity and dopamine transporters in the striatum and substantia nigra pars compacta (SNc) from 3- to 56-days postlesion (dpl). Increased binding of TSPO ligands used, i.e., [(3)H]PK11195 and [(125)I]CLINDE, was observed in the lesioned striatum at 3, 7, and 14 dpl, followed by a progressive return to the basal level at 56 dpl. The binding profile in the SNc showed progressive binding beginning at 3 dpl, peaking at 14 dpl, and progressively decreasing until 56 dpl. In this model, the neuroinflammatory and neurodegenerative processes occurred concomitantly. The transitory occurrence of microglial activation could be involved in the lasting installation of dopaminergic neuron loss.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal
  • Carrier Proteins / metabolism
  • Corpus Striatum / metabolism
  • Corpus Striatum / pathology*
  • Corpus Striatum / physiopathology
  • Disease Models, Animal
  • Dopaminergic Neurons / metabolism*
  • Inflammation / chemically induced
  • Inflammation / pathology
  • Inflammation / physiopathology
  • Longitudinal Studies
  • Microglia / metabolism
  • Nerve Degeneration / chemically induced
  • Nerve Degeneration / pathology
  • Nerve Degeneration / physiopathology
  • Parkinson Disease / metabolism
  • Parkinson Disease / pathology*
  • Parkinson Disease / physiopathology
  • Rats
  • Rats, Wistar
  • Receptors, GABA-A / metabolism
  • Substantia Nigra / metabolism
  • Substantia Nigra / pathology
  • Time Factors

Substances

  • Carrier Proteins
  • Receptors, GABA-A
  • Tspo protein, rat