Impaired hepatic function and central dopaminergic denervation in a rodent model of Parkinson's disease: A self-perpetuating crosstalk?

Mariapia Vairetti, Andrea Ferrigno, Vittoria Rizzo, Giulia Ambrosi, Alberto Bianchi, Plinio Richelmi, Fabio Blandini, Marie Therese Armentero

Research output: Contribution to journalArticle

Abstract

In Parkinson's disease (PD), aside from the central lesion, involvement of visceral organs has been proposed as part of the complex clinical picture of the disease. The issue is still poorly understood and relatively unexplored. In this study we used a classic rodent model of nigrostriatal degeneration, induced by the intrastriatal injection of 6-hydroxydopamine (6-OHDA), to investigate whether and how a PD-like central dopaminergic denervation may influence hepatic functions. Rats received an intrastriatal injection of 6-OHDA or saline (sham), and blood, cerebrospinal fluid, liver and brain samples were obtained for up to 8. weeks after surgery. Specimens were analyzed for changes in cytokine and thyroid hormone levels, as well as liver mitochondrial alterations. Hepatic mitochondria isolated from animals bearing extended nigrostriatal lesion displayed increased ROS production, while membrane potential (δΨ) and ATP production were significantly decreased. Reduced ATP production correlated with nigral neuronal loss. Thyroid hormone levels were significantly increased in serum of PD rats compared to sham animals while steady expression of selected cytokines was detected in all groups. Hepatic enzyme functions were comparable in all animals. Our study indicates for the first time that in a rodent model of PD, hepatic mitochondria dysfunctions arise as a consequence of nigrostriatal degeneration, and that thyroid hormone represents a key interface in this CNS-liver interaction. Liver plays a fundamental detoxifying function and a better understanding of PD-related hepatic mitochondrial alterations, which might further promote neurodegeneration, may represent an important step for the development of novel therapeutic strategies.

Original languageEnglish
Pages (from-to)176-184
Number of pages9
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1822
Issue number2
DOIs
Publication statusPublished - Feb 2012

Keywords

  • 6-OHDA
  • ATP
  • Liver
  • Membrane potential
  • Mitochondrion
  • Thyroid hormone

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine

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