N-Acetylaspartate Drives Oligodendroglial Differentiation via Histone Deacetylase Activation
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 neurodegenera...
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| Format: | Article |
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MDPI AG
2023-07-01
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| Online Access: | https://www.mdpi.com/2073-4409/12/14/1861 |
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| author | Alessandra Dominicis Alice Del Giovane Matteo Torreggiani Antonella Damiana Recchia Fabio Ciccarone Maria Rosa Ciriolo Antonella Ragnini-Wilson |
| author_facet | Alessandra Dominicis Alice Del Giovane Matteo Torreggiani Antonella Damiana Recchia Fabio Ciccarone Maria Rosa Ciriolo Antonella Ragnini-Wilson |
| author_sort | Alessandra Dominicis |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T01:13:01Z |
| format | Article |
| id | doaj.art-ca4a24bd878b48c6a044ae1c0debb113 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T01:13:01Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-ca4a24bd878b48c6a044ae1c0debb1132023-11-18T18:46:13ZengMDPI AGCells2073-44092023-07-011214186110.3390/cells12141861N-Acetylaspartate Drives Oligodendroglial Differentiation via Histone Deacetylase ActivationAlessandra Dominicis0Alice Del Giovane1Matteo Torreggiani2Antonella Damiana Recchia3Fabio Ciccarone4Maria Rosa Ciriolo5Antonella Ragnini-Wilson6Department of Biology, University of Rome Tor Vergata, 00133 Rome, ItalyDepartment of Biology, University of Rome Tor Vergata, 00133 Rome, ItalyDepartment of Biology, University of Rome Tor Vergata, 00133 Rome, ItalyDepartment of Biology, University of Rome Tor Vergata, 00133 Rome, ItalyDepartment of Biology, University of Rome Tor Vergata, 00133 Rome, ItalyDepartment of Biology, University of Rome Tor Vergata, 00133 Rome, ItalyDepartment of Biology, University of Rome Tor Vergata, 00133 Rome, ItalyAn 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.https://www.mdpi.com/2073-4409/12/14/1861remyelinationepigeneticshistone deacetylases (HDACs)multiple sclerosis (MS)N-acetylaspartate (NAA)neurodegeneration |
| spellingShingle | Alessandra Dominicis Alice Del Giovane Matteo Torreggiani Antonella Damiana Recchia Fabio Ciccarone Maria Rosa Ciriolo Antonella Ragnini-Wilson N-Acetylaspartate Drives Oligodendroglial Differentiation via Histone Deacetylase Activation Cells remyelination epigenetics histone deacetylases (HDACs) multiple sclerosis (MS) N-acetylaspartate (NAA) neurodegeneration |
| title | N-Acetylaspartate Drives Oligodendroglial Differentiation via Histone Deacetylase Activation |
| title_full | N-Acetylaspartate Drives Oligodendroglial Differentiation via Histone Deacetylase Activation |
| title_fullStr | N-Acetylaspartate Drives Oligodendroglial Differentiation via Histone Deacetylase Activation |
| title_full_unstemmed | N-Acetylaspartate Drives Oligodendroglial Differentiation via Histone Deacetylase Activation |
| title_short | N-Acetylaspartate Drives Oligodendroglial Differentiation via Histone Deacetylase Activation |
| title_sort | n acetylaspartate drives oligodendroglial differentiation via histone deacetylase activation |
| topic | remyelination epigenetics histone deacetylases (HDACs) multiple sclerosis (MS) N-acetylaspartate (NAA) neurodegeneration |
| url | https://www.mdpi.com/2073-4409/12/14/1861 |
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