Neuroprotective potential of adenosine A2A and cannabinoid CB1 receptor antagonists in an animal model of Parkinson disease

Silvia Cerri, Giovanna Levandis, Giulia Ambrosi, Elena Montepeloso, Gian Filippo Antoninetti, Rafael Franco, José Luis Lanciego, Younis Baqi, Christa E. Müller, Annalisa Pinna, Fabio Blandini, Marie Therese Armentero*

*Corresponding author for this work

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

The development of nondopaminergic therapeutic strategies that may improve motor and nonmotor deficits, while possibly slowing down the neurodegenerative process and associated neuroinflammation, is a primary goal of Parkinson disease (PD) research. We investigated the neuroprotective and anti-inflammatory potential of combined and single treatment with adenosine A2A and cannabinoid CB1 receptor antagonists MSX-3 and rimonabant, respectively, in a rodent model of PD. Rats bearing a unilateral intrastriatal 6-hydroxydopamine lesion were treated chronically with MSX-3 (0.5or 1 mg/kg/d) and rimonabant (0.1 mg/kg/d) given as monotherapy or combined. The effects of the treatments to counteract dopaminergic cell death and neuroinflammation were assessed by immunohistochemistry for tyrosine hydroxylase and glial cell markers, respectively. Both rimonabant and MSX-3 (1 mg/kg/d) promoted dopaminergic neuron survival in the substantia nigra pars compacta (SNc) when given alone; this effect was weakened when the compounds were combined. Glial activation was not significantly affected by MSX-3 (1 mg/kg/d), whereas rimonabant seemed to increase astrocyte cell density in the SNc. Our findings demonstrate the neuroprotective potential of single treatments and suggest that glial cells might be involved in this protective effect. The results also indicate that the neuroprotective potential of combined therapy may not necessarily reflect or promote single-drug effects and point out that special care should be taken when considering multidrug therapies in PD.

Original languageEnglish
Pages (from-to)414-424
Number of pages11
JournalJournal of Neuropathology and Experimental Neurology
Volume73
Issue number5
DOIs
Publication statusPublished - 2014

Keywords

  • 6-Hydroxydopamine
  • Dopamine
  • Glial cells
  • Neurodegeneration
  • Neuroinflammation
  • Neuroprotection
  • Receptor heteromer

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Neurology
  • Cellular and Molecular Neuroscience

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