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Homeostatic changes of the endocannabinoid system in Parkinson's disease

Authors

  • Valerio Pisani MD,

    1. Department of Neuroscience, University of Rome Tor Vergata, Rome, Italy
    2. Neurophysiology Lab, Fondazione Santa Lucia IRCCS, Rome, Italy
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    • Valerio Pisani and Graziella Madeo contributed equally to this work.

  • Graziella Madeo MD,

    1. Department of Neuroscience, University of Rome Tor Vergata, Rome, Italy
    2. Neurophysiology Lab, Fondazione Santa Lucia IRCCS, Rome, Italy
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    • Valerio Pisani and Graziella Madeo contributed equally to this work.

  • Annalisa Tassone PhD,

    1. Department of Neuroscience, University of Rome Tor Vergata, Rome, Italy
    2. Neurophysiology Lab, Fondazione Santa Lucia IRCCS, Rome, Italy
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  • Giuseppe Sciamanna PhD,

    1. Department of Neuroscience, University of Rome Tor Vergata, Rome, Italy
    2. Neurophysiology Lab, Fondazione Santa Lucia IRCCS, Rome, Italy
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  • Mauro Maccarrone MD, PhD,

    1. Neurophysiology Lab, Fondazione Santa Lucia IRCCS, Rome, Italy
    2. Department of Biomedical Sciences, University of Teramo, Italy
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  • Paolo Stanzione MD,

    1. Department of Neuroscience, University of Rome Tor Vergata, Rome, Italy
    2. Neurophysiology Lab, Fondazione Santa Lucia IRCCS, Rome, Italy
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  • Antonio Pisani MD

    Corresponding author
    1. Department of Neuroscience, University of Rome Tor Vergata, Rome, Italy
    2. Neurophysiology Lab, Fondazione Santa Lucia IRCCS, Rome, Italy
    • Department of Neuroscience, University of Rome “Tor Vergata” Via Montpellier 1, 00133, Rome, Italy
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  • Relevant conflict of interest/financial disclosures: Nothing to report.

    This investigation was supported by grants from Ministero Istruzione, Università e Ricerca, and by Ministero Salute (Progetto Finalizzato) to AP, by Fondazione TERCAS to MM, and by INAIL to AP.

Abstract

Endocannabinoids (eCBs) are endogenous lipids that bind principally type-1 and type-2 cannabinoid (CB1 and CB2) receptors. N-Arachidonoylethanolamine (AEA, anandamide) and 2-arachidonoylglycerol (2-AG) are the best characterized eCBs that are released from membrane phospholipid precursors through multiple biosynthetic pathways. Together with their receptors and metabolic enzymes, eCBs form the so-called “eCB system”. The later has been involved in a wide variety of actions, including modulation of basal ganglia function. Consistently, both eCB levels and CB1 receptor expression are high in several basal ganglia regions, and more specifically in the striatum and in its target projection areas. In these regions, the eCB system establishes a close functional interaction with dopaminergic neurotransmission, supporting a relevant role for eCBs in the control of voluntary movements. Accordingly, compelling experimental and clinical evidence suggests that a profound rearrangement of the eCB system in the basal ganglia follows dopamine depletion, as it occurs in Parkinson's disease (PD).

In this article, we provide a brief survey of the evidence that the eCB system changes in both animal models of, and patients suffering from, PD. A striking convergence of findings is observed between both rodent and primate models and PD patients, indicating that the eCB system undergoes dynamic, adaptive changes, aimed at restoring an apparent homeostasis within the basal ganglia network. © 2010 Movement Disorder Society

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