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N-Acetylaspartate Drives Oligodendroglial Differentiation via Histone Deacetylase Activation.
Dominicis, Alessandra; Del Giovane, Alice; Torreggiani, Matteo; Recchia, Antonella Damiana; Ciccarone, Fabio; Ciriolo, Maria Rosa; Ragnini-Wilson, Antonella.
Affiliation
  • Dominicis A; Department of Biology, University of Rome Tor Vergata, 00133 Rome, Italy.
  • Del Giovane A; Department of Biology, University of Rome Tor Vergata, 00133 Rome, Italy.
  • Torreggiani M; Department of Biology, University of Rome Tor Vergata, 00133 Rome, Italy.
  • Recchia AD; Department of Biology, University of Rome Tor Vergata, 00133 Rome, Italy.
  • Ciccarone F; Department of Biology, University of Rome Tor Vergata, 00133 Rome, Italy.
  • Ciriolo MR; IRCCS San Raffaele, 00166 Rome, Italy.
  • Ragnini-Wilson A; Department of Biology, University of Rome Tor Vergata, 00133 Rome, Italy.
Cells ; 12(14)2023 07 14.
Article in En | MEDLINE | ID: mdl-37508525
ABSTRACT
An unmet clinical goal in demyelinating pathologies is to restore the myelin sheath prior to neural degeneration. N-acetylaspartate (NAA) is an acetylated derivative form of aspartate, abundant in the healthy brain but severely reduced during traumatic brain injury and in patients with neurodegenerative pathologies. How extracellular NAA variations impact the remyelination process and, thereby, the ability of oligodendrocytes to remyelinate axons remains unexplored. Here, we evaluated the remyelination properties of the oligodendroglial (OL) mouse cell line Oli-neuM under different concentrations of NAA using a combination of biochemical, qPCR, immunofluorescence assays, and in vitro engagement tests, at NAA doses compatible with those observed in healthy brains and during brain injury. We observed that oligodendroglia cells respond to decreasing levels of NAA by stimulating differentiation and promoting gene expression of myelin proteins in a temporally regulated manner. Low doses of NAA potently stimulate Oli-neuM to engage with synthetic axons. Furthermore, we show a concentration-dependent expression of specific histone deacetylases essential for MBP gene expression under NAA or Clobetasol treatment. These data are consistent with the idea that oligodendrocytes respond to lowering the NAA concentration by activating the remyelination process via deacetylase activation.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Aspartic Acid / Histone Deacetylases Limits: Animals Language: En Journal: Cells Year: 2023 Document type: Article Affiliation country: Italy

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Aspartic Acid / Histone Deacetylases Limits: Animals Language: En Journal: Cells Year: 2023 Document type: Article Affiliation country: Italy