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2-Arachidonoylglycerol Reduces Proteoglycans and Enhances Remyelination in a Progressive Model of Demyelination

AuthorsFeliú, Ana; Bonilla del Río, Itziar; Carrillo-Salinas, Francisco; Hernández-Torres, Gloria; Puente, Nagore; Ortega-Gutiérrez, S.; López-Rodríguez, María L.; Grandes, Pedro; Mecha, Miriam ; Guaza, Carmen
Chondroitin sulfate proteoglycans
Issue Date30-Aug-2017
PublisherSociety for Neuroscience
CitationJournal of Neuroscience 37(35): 8385-8398 (2017)
AbstractThe failure to undergo remyelination is a critical impediment to recovery in multiple sclerosis. Chondroitin sulfate proteoglycans (CSPGs) accumulate at demyelinating lesions creating a nonpermissive environment that impairs axon regeneration and remyelination. Here, we reveal a new role for 2-arachidonoylglycerol (2-AG), the major CNS endocannabinoid, in the modulation of CSPGs deposition in a progressive model of multiple sclerosis, the Theiler's murine encephalomyelitis virus-induced demyelinating disease. Treatment with a potent reversible inhibitor of the enzyme monoacylglycerol lipase, which accounts for 85% of the 2-AG degradation in the mouse CNS, modulates neuroinflammation and reduces CSPGs accumulation and astrogliosis around demyelinated lesions in the spinal cord of Theiler's murine encephalomyelitis virus-infected mice. Inhibition of 2-AG hydrolysis augments the number of mature oligodendrocytes and increases MBP, leading to remyelination and functional recovery of mice. Our findings establish a mechanism for 2-AG promotion of remyelination with implications in axonal repair in CNS demyelinating pathologies.
Publisher version (URL)https://doi.org/10.1523/JNEUROSCI.2900-16.2017
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