Dataset Information

N-Acetylaspartate Drives Oligodendroglial Differentiation via Histone Deacetylase Activation.

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.

SUBMITTER: Dominicis A

PROVIDER: S-EPMC10378218 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

N-Acetylaspartate Drives Oligodendroglial Differentiation via Histone Deacetylase Activation.

Dominicis Alessandra A Del Giovane Alice A Torreggiani Matteo M Recchia Antonella Damiana AD Ciccarone Fabio F Ciriolo Maria Rosa MR Ragnini-Wilson Antonella A

Cells 20230714 14

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 remyel ...[more]

PMID: 37508525

Similar Datasets

Project description:Background and purposeSepsis is a systemic inflammatory response accompanied by excessive production of inflammatory cytokines and cardiovascular dysfunction. Importantly, macrophage-derived pro-inflammatory agents play a key role in cardiovascular impairment in sepsis. Here we have investigated the effects of trimetazidine (TMZ) on pro-inflammatory responses of macrophages in endotoxin-induced myocardial dysfunction.Experimental approachMice pretreated with TMZ were injected i.p. with LPS and cardiac function evaluated. Levels of macrophage infiltration, macrophage inflammatory response and cardiomyocyte apoptosis were measured using immunohistochemical staining, elisa, real-time RT-PCR, Western blot, TUNEL and flow cytometry assays.Key resultsPretreatment with TMZ prevented LPS-induced myocardial dysfunction and apoptosis. TMZ also lowered levels of pro-inflammatory cytokines in serum and cardiac tissue and myocardial macrophage infiltration. Bone marrow transplantation indicated that TMZ alleviated LPS-induced myocardial dysfunction via decreasing macrophage infiltration. TMZ reduced expression of pro-inflammatory cytokines in LPS-stimulated cardiac and peritoneal macrophages. Co-culture of TMZ-pretreated macrophages with cardiomyocytes and conditioned media from TMZ-pretreated macrophages both decreased LPS-induced cardiomyocyte apoptosis. The anti-apoptosis effects of TMZ resulted from decrease of pro-inflammatory cytokines, partly due to normalizing the sirtuin 1 (Sirt1)/AMP-activated protein kinase (AMPK)/Nrf2/haem oxygenase-1 and Sirt1/PPARα pathways in macrophages. Cytokine secretion was also regulated by ROS, which were attenuated by TMZ via activation of Sirt1, AMPK and PPARα.Conclusions and implicationsTMZ protected against LPS-induced myocardial dysfunction and apoptosis, accompanied by inhibition of macrophage pro-inflammatory responses. Our studies suggest that TMZ might represent a novel therapeutic agent to prevent and treat sepsis-induced myocardial dysfunction.

Dataset Information

N-Acetylaspartate Drives Oligodendroglial Differentiation via Histone Deacetylase Activation.

Publications

N-Acetylaspartate Drives Oligodendroglial Differentiation via Histone Deacetylase Activation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets