Quinolinic acid induced neurodegeneration in the striatum: A combined in vivo and in vitro analysis of receptor changes and microglia activation

R. M. Moresco, T. Lavazza, S. Belloli, M. Lecchi, A. Pezzola, S. Todde, M. Matarrese, A. Carpinelli, E. Turolla, V. Zimarino, P. Popoli, A. Malgaroli, F. Fazio

Research output: Contribution to journalArticle

Abstract

Purpose: Huntington's disease (HD) is a progressive neurodegenerative disorder, which is characterised by prominent neuronal cell loss in the basal ganglia with motor and cognitive disturbances. One of the most well-studied pharmacological models of HD is produced by local injection in the rat brain striatum of the excitotoxin quinolinic acid (QA), which produces many of the distinctive features of this human neurodegenerative disorder. Here, we report a detailed analysis, obtained both in vivo and in vitro of this pharmacological model of HD. Materials and methods: By combining emission tomography (PET) with autoradiographic and immunocytochemical confocal laser techniques, we quantified in the QA-injected striatum the temporal behavior (from 1 to 60 days from the excitotoxic insult) of neuronal cell density and receptor availability (adenosine A2A and dopamine D2 receptors) together with the degree of microglia activation. Results: Both approaches showed a loss of adenosine A2A and dopamine D2 receptors paralleled by an increase of microglial activation. Conclusion: This combined longitudinal analysis of the disease progression, which suggested an impairment of neurotransmission, neuronal integrity and a reversible activation of brain inflammatory processes, might represent a more quantitative approach to compare the differential effects of treatments in slowing down or reversing HD in rodent models with potential applications to human patients.

Original languageEnglish
Pages (from-to)704-715
Number of pages12
JournalEuropean Journal of Nuclear Medicine and Molecular Imaging
Volume35
Issue number4
DOIs
Publication statusPublished - Apr 2008

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Keywords

  • Adenosine A receptor
  • Dopamine D receptor
  • Emission tomography
  • Huntington's disease
  • Striatum

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Radiological and Ultrasound Technology

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