Abstract
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+/Ca2+ exchanger NCX3. While blocking NMDA or NCX3 significantly prevented D-Aspartate-induced [Ca2+]i oscillations, blocking AMPA and glutamate transporters prevented both the initial and oscillatory [Ca2+]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.
| Original language | English |
|---|---|
| Article number | e9278 |
| Journal | EMBO Molecular Medicine |
| Volume | 11 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jan 1 2019 |
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Keywords
- cuprizone
- D-Aspartate
- NCX3
- oligodendrocytes
- remyelination
ASJC Scopus subject areas
- Molecular Medicine
Cite this
D-Aspartate treatment attenuates myelin damage and stimulates myelin repair. / de 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.
In: EMBO Molecular Medicine, Vol. 11, No. 1, e9278, 01.01.2019.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - D-Aspartate treatment attenuates myelin damage and stimulates myelin repair
AU - de Rosa, Valeria
AU - Secondo, Agnese
AU - Pannaccione, Anna
AU - Ciccone, Roselia
AU - Formisano, Luigi
AU - Guida, Natascia
AU - Crispino, Roberta
AU - Fico, Annalisa
AU - Polishchuk, Roman
AU - D'Aniello, Antimo
AU - Annunziato, Lucio
AU - Boscia, Francesca
PY - 2019/1/1
Y1 - 2019/1/1
N2 - 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+/Ca2+ exchanger NCX3. While blocking NMDA or NCX3 significantly prevented D-Aspartate-induced [Ca2+]i oscillations, blocking AMPA and glutamate transporters prevented both the initial and oscillatory [Ca2+]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.
AB - 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+/Ca2+ exchanger NCX3. While blocking NMDA or NCX3 significantly prevented D-Aspartate-induced [Ca2+]i oscillations, blocking AMPA and glutamate transporters prevented both the initial and oscillatory [Ca2+]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.
KW - cuprizone
KW - D-Aspartate
KW - NCX3
KW - oligodendrocytes
KW - remyelination
UR - http://www.scopus.com/inward/record.url?scp=85058687017&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85058687017&partnerID=8YFLogxK
U2 - 10.15252/emmm.201809278
DO - 10.15252/emmm.201809278
M3 - Article
C2 - 30559305
AN - SCOPUS:85058687017
VL - 11
JO - EMBO Molecular Medicine
JF - EMBO Molecular Medicine
SN - 1757-4676
IS - 1
M1 - e9278
ER -