N-docosahexaenoylethanolamine Stimulates Axon Outgrowth and Regeneration After Injury

Authors

• HS Kwon
• HY Kim

Abstract

N-docosahexaenoylethanolamine (synaptamide), a structural analog of the cannabinoid receptor ligand anandamide, is an endogenous metabolite of docosahexaenoic acid (DHA). Our previous studies have shown that synaptamide stimulates neurite growth, synaptogenesis and glutamatergic synaptic activity, promoting neurodevelopment. In this study, we investigated the effect of synaptamide on axon growth and regeneration after injury. For in vitro studies, mouse P0 primary cortical neurons were plated on an axon chamber and axotomy was performed on 7DIV when axons were sufficiently grown into the other side of the axon chamber. To investigate axon regeneration in vivo, synaptamide (10-25 mg/kg) was injected intravitreally into mice at 12-14 week of age after optic nerve crush (ONC). At 10nM concentrations, synaptamide promoted axon outgrowth through the protein kinase A (PKA) signaling pathway. Significant increases of axon growth and axon cone formation were observed when synaptamide was added to either soma or axon side of the chamber. Axon growth after axotomy was also promoted by synaptamide addition to either side of the chamber. Using bodipy-synaptamide and GPR110 antibody, direct physical interaction of synaptamide and GPR110 in primary cortical neuron was demonstrated, and this interaction was crucial for the observed axon outgrowth.In the ONC animal model, axon regeneration was promoted after synaptamide injection. These findings suggest synaptamides an endogenous metabolite of therapeutic potential for functional recovery after brain injury.

Scientific Focus Area: Neuroscience

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