Type your tag names separated by a space and hit enter

Administration of 2-arachidonoylglycerol ameliorates both acute and chronic experimental autoimmune encephalomyelitis.

Abstract

BACKGROUND AND PURPOSE

Experimental autoimmune encephalomyelitis (EAE) is a widely used model of multiple sclerosis (MS) and both conditions have been reported to exhibit reduced endocannabinoid activity. The purpose of this study was to address the effect of exogenously administered 2-arachidonoylglycerol (2AG), an endocannabinoid receptor ligand, on acute phase and chronic disability in EAE.

EXPERIMENTAL APPROACH

Acute and chronic EAE models were induced in susceptible mice and 2AG-treatment was applied for 14 days from day of disease induction.

KEY RESULTS

2AG-treatment ameliorated acute phase of disease with delay of disease onset in both EAE models and reduced disease mortality and long-term (70 days post-induction) clinical disability in chronic EAE. Reduced axonal pathology in the chronic EAE- (p<0.0001) and increased activation and ramification of microglia in the 2AG-treated acute EAE- (p<0.05) model were noticed. The latter was accompanied by a 2- to 4-fold increase of the M2-macrophages in the perivascular infiltrations (p<0.001) of the 2AG-treated animals in the acute (day 22), although not the chronic (day 70), EAE model. Expression of cannabinoid receptors 1 (CB1R) and 2 (CB2R) was increased in 2AG-treated animals of acute EAE vs. controls (p<0.05). In addition, ex vivo viability assays exhibited reduced proliferation of activated lymph node cells when extracted from 2AG-treated EAE animals, whereas a dose-dependent response of activated lymphocytes to 2AG-treatment in vitro was noticed.

CONCLUSION AND IMPLICATIONS

Our data indicate for the first time that 2AG treatment may provide direct (via CBRs) and immune (via M2 macrophages) mediated neuroprotection in EAE.

Links

  • Publisher Full Text
  • Authors+Show Affiliations

    ,

    Laboratory of Experimental Neurology and Neuroimmunology, B' Department of Neurology, AHEPA University Hospital Aristotle University, Thessaloniki 54636, Macedonia, Greece.

    , , , , , , , , , , ,

    Source

    Brain research 1390: 2011 May 16 pg 126-41

    MeSH

    Acute Disease
    Animals
    Arachidonic Acids
    Chronic Disease
    Disease Models, Animal
    Encephalomyelitis, Autoimmune, Experimental
    Endocannabinoids
    Female
    Glycerides
    Mice
    Mice, Inbred C57BL
    Random Allocation

    Pub Type(s)

    Comparative Study
    Journal Article
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    21406188

    Citation

    * When formatting your citation, note that all book, journal, and database titles should be italicized* Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Administration of 2-arachidonoylglycerol ameliorates both acute and chronic experimental autoimmune encephalomyelitis. AU - Lourbopoulos,Athanasios, AU - Grigoriadis,Nikolaos, AU - Lagoudaki,Roza, AU - Touloumi,Olga, AU - Polyzoidou,Eleni, AU - Mavromatis,Ioannis, AU - Tascos,Nikolaos, AU - Breuer,Aviva, AU - Ovadia,Haim, AU - Karussis,Dimitris, AU - Shohami,Ester, AU - Mechoulam,Raphael, AU - Simeonidou,Constantina, Y1 - 2011/03/13/ PY - 2010/11/07/received PY - 2011/03/04/revised PY - 2011/03/08/accepted PY - 2011/3/17/entrez PY - 2011/3/17/pubmed PY - 2012/3/8/medline SP - 126 EP - 41 JF - Brain research JO - Brain Res. VL - 1390 N2 - BACKGROUND AND PURPOSE: Experimental autoimmune encephalomyelitis (EAE) is a widely used model of multiple sclerosis (MS) and both conditions have been reported to exhibit reduced endocannabinoid activity. The purpose of this study was to address the effect of exogenously administered 2-arachidonoylglycerol (2AG), an endocannabinoid receptor ligand, on acute phase and chronic disability in EAE. EXPERIMENTAL APPROACH: Acute and chronic EAE models were induced in susceptible mice and 2AG-treatment was applied for 14 days from day of disease induction. KEY RESULTS: 2AG-treatment ameliorated acute phase of disease with delay of disease onset in both EAE models and reduced disease mortality and long-term (70 days post-induction) clinical disability in chronic EAE. Reduced axonal pathology in the chronic EAE- (p<0.0001) and increased activation and ramification of microglia in the 2AG-treated acute EAE- (p<0.05) model were noticed. The latter was accompanied by a 2- to 4-fold increase of the M2-macrophages in the perivascular infiltrations (p<0.001) of the 2AG-treated animals in the acute (day 22), although not the chronic (day 70), EAE model. Expression of cannabinoid receptors 1 (CB1R) and 2 (CB2R) was increased in 2AG-treated animals of acute EAE vs. controls (p<0.05). In addition, ex vivo viability assays exhibited reduced proliferation of activated lymph node cells when extracted from 2AG-treated EAE animals, whereas a dose-dependent response of activated lymphocytes to 2AG-treatment in vitro was noticed. CONCLUSION AND IMPLICATIONS: Our data indicate for the first time that 2AG treatment may provide direct (via CBRs) and immune (via M2 macrophages) mediated neuroprotection in EAE. SN - 1872-6240 UR - https://www.unboundmedicine.com/medline/citation/21406188/abstract/Administration_of_2_arachidonoylglycerol_ameliorates_both_acute_and_chronic_Experimental_Autoimmune_Encephalomyelitis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-8993(11)00517-8 DB - PRIME DP - Unbound Medicine ER -