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

• DOI: 10.1523/jneurosci.2900-16.2017
• Publication Date: 2017-07-28T01:00:39Z
• Authors: Ana Feliú; Itziar Bonilla de...; Francisco Javier ...; Gloria Hernández-...; Leyre Mestre; Nagore Puente; Silvia Ortega-Gut...; Maria L. López-Ro...; Pedro Grandes; Miriam Mecha; Carmen Guaza
• Keywords: Remyelination; 2-Arachidonoylglycerol; Encephalomyelitis

The failure to undergo remyelination is a critical impediment recovery in multiple sclerosis. Chondroitin sulfate proteoglycans (CSPGs) accumulate at demyelinating lesions creating nonpermissive environment that impairs axon regeneration and remyelination. Here, we reveal new role for 2-arachidonoylglycerol (2-AG), the major CNS endocannabinoid, modulation of CSPGs deposition progressive model sclerosis, Theiler9s murine encephalomyelitis virus-induced disease. Treatment with potent reversible inhibitor enzyme monoacylglycerol lipase, which accounts 85% 2-AG degradation mouse CNS, modulates neuroinflammation reduces accumulation astrogliosis around demyelinated spinal cord virus-infected mice. Inhibition hydrolysis augments number mature oligodendrocytes increases MBP, leading functional Our findings establish mechanism promotion implications axonal repair pathologies. <b>SIGNIFICANCE STATEMENT</b> chondroitin contributes associated Here unveil 2-arachidonoylglycerol, proteoglycan treatment during chronic phase increased tone promotes sclerosis ameliorating motor dysfunction.