D-Aspartate treatment attenuates myelin damage and stimulates myelin repair

Valeria de Rosa, Agnese Secondo, Anna Pannaccione, Roselia Ciccone, Luigi Formisano, Natascia Guida, Roberta Crispino, Annalisa Fico, Roman Polishchuk, Antimo D'Aniello, Lucio Annunziato, Francesca Boscia

Research output: Contribution to journalArticle

2 Citations (Scopus)

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 languageEnglish
Article numbere9278
JournalEMBO Molecular Medicine
Volume11
Issue number1
DOIs
Publication statusPublished - Jan 1 2019

Fingerprint

D-Aspartic Acid
Myelin Sheath
Oligodendroglia
Amino Acid Transport System X-AG
Glutamate Receptors
N-Methyl-D-Aspartate Receptors
Synapses
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
AMPA Receptors
Demyelinating Diseases
N-Methylaspartate
Axons
Regeneration
Glutamic Acid
Schizophrenia
Inflammation
Neurons
Amino Acids

Keywords

  • cuprizone
  • D-Aspartate
  • NCX3
  • oligodendrocytes
  • remyelination

ASJC Scopus subject areas

  • Molecular Medicine

Cite this

de Rosa, V., Secondo, A., Pannaccione, A., Ciccone, R., Formisano, L., Guida, N., ... Boscia, F. (2019). D-Aspartate treatment attenuates myelin damage and stimulates myelin repair. EMBO Molecular Medicine, 11(1), [e9278]. https://doi.org/10.15252/emmm.201809278

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 journalArticle

de Rosa, V, Secondo, A, Pannaccione, A, Ciccone, R, Formisano, L, Guida, N, Crispino, R, Fico, A, Polishchuk, R, D'Aniello, A, Annunziato, L & Boscia, F 2019, 'D-Aspartate treatment attenuates myelin damage and stimulates myelin repair', EMBO Molecular Medicine, vol. 11, no. 1, e9278. https://doi.org/10.15252/emmm.201809278
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. / D-Aspartate treatment attenuates myelin damage and stimulates myelin repair. In: EMBO Molecular Medicine. 2019 ; Vol. 11, No. 1.
@article{6a9c2fdc639a4820a1c05f573cf30923,
title = "D-Aspartate treatment attenuates myelin damage and stimulates myelin repair",
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.",
keywords = "cuprizone, D-Aspartate, NCX3, oligodendrocytes, remyelination",
author = "{de Rosa}, Valeria and Agnese Secondo and Anna Pannaccione and Roselia Ciccone and Luigi Formisano and Natascia Guida and Roberta Crispino and Annalisa Fico and Roman Polishchuk and Antimo D'Aniello and Lucio Annunziato and Francesca Boscia",
year = "2019",
month = "1",
day = "1",
doi = "10.15252/emmm.201809278",
language = "English",
volume = "11",
journal = "EMBO Molecular Medicine",
issn = "1757-4676",
publisher = "Wiley-Blackwell",
number = "1",

}

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 -