Open AccessD‐Aspartate treatment attenuates myelin damage and stimulates myelin repair
Author(s) -
Rosa Valeria,
Secondo Agnese,
Pannaccione Anna,
Ciccone Roselia,
Formisano Luigi,
Guida Natascia,
Crispino Roberta,
Fico Annalisa,
Polishchuk Roman,
D'Aniello Antimo,
Annunziato Lucio,
Boscia Francesca
Publication year - 2019
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201809278
Subject(s) - myelin , myelin sheath , chemistry , microbiology and biotechnology , medicine , immunology , neuroscience , biology , central nervous system
Glutamate signaling may orchestrate oligodendrocyte precursor cell ( OPC ) development and myelin regeneration through the activation of glutamate receptors at OPC ‐neuron synapses. D‐Aspartate is a D‐amino acid exerting modulatory actions at glutamatergic synapses. Chronic administration of D‐Aspartate has been proposed as therapeutic treatment in diseases related to myelin dysfunction and NMDA receptors hypofunction, including schizophrenia and cognitive deficits. Here, we show, by using an in vivo remyelination model, that administration of D‐Aspartate during remyelination improved motor coordination, accelerated myelin recovery, and significantly increased the number of small‐diameter myelinated axons. Chronically administered during demyelination, D‐Aspartate also attenuated myelin loss and inflammation. Interestingly, D‐Aspartate exposure stimulated OPC maturation and accelerated developmental myelination in organotypic cerebellar slices. D‐Aspartate promoting effects on OPC maturation involved the activation of glutamate transporters, AMPA and NMDA receptors, and the Na + /Ca 2+ exchanger NCX 3. While blocking NMDA or NCX 3 significantly prevented D‐Aspartate‐induced [Ca 2+ ] i oscillations, blocking AMPA and glutamate transporters prevented both the initial and oscillatory [Ca 2+ ] i response as well as D‐Aspartate‐induced inward currents in OPC . Our findings reveal that D‐Aspartate treatment may represent a novel strategy for promoting myelin recovery.