Next Article in Journal
Avian Expression Patterns and Genomic Mapping Implicate Leptin in Digestion and TNF in Immunity, Suggesting That Their Interacting Adipokine Role Has Been Acquired Only in Mammals
Next Article in Special Issue
L-Alanine Exporter, AlaE, of Escherichia coli Functions as a Safety Valve to Enhance Survival under Feast Conditions
Previous Article in Journal
Fucoxanthin-Rich Brown Algae Extract Improves Male Reproductive Function on Streptozotocin-Nicotinamide-Induced Diabetic Rat Model
Previous Article in Special Issue
Mitochondrial Carriers for Aspartate, Glutamate and Other Amino Acids: A Review
Open AccessArticle

Deficiency of Mitochondrial Aspartate-Glutamate Carrier 1 Leads to Oligodendrocyte Precursor Cell Proliferation Defects Both In Vitro and In Vivo

1
Department of Pharmacy and BioTechnology, University of Bologna, 40126 Bologna, Italy
2
Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, 70121 Bari, Italy
3
Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology, Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, 44121 Ferrara, Italy
4
Department of Experimental, Diagnostic and Specialty Medicine (DIMES, Dipartimento di Medicina Specialistica Diagnostica e Sperimentale) and C.I.G. Interdepartmental Centre “L. Galvani”, University of Bologna, 40126 Bologna, Italy
5
Maria Cecilia Hospital, GVM Care & Research, Cotignola, 48010 Ravenna, Italy
6
Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies IBIOM, CNR, 70126 Bari, Italy
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(18), 4486; https://doi.org/10.3390/ijms20184486
Received: 30 July 2019 / Revised: 4 September 2019 / Accepted: 6 September 2019 / Published: 11 September 2019
(This article belongs to the Special Issue Amino Acids Transport and Metabolism 2.0)
Aspartate-Glutamate Carrier 1 (AGC1) deficiency is a rare neurological disease caused by mutations in the solute carrier family 25, member 12 (SLC25A12) gene, encoding for the mitochondrial aspartate-glutamate carrier isoform 1 (AGC1), a component of the malate–aspartate NADH shuttle (MAS), expressed in excitable tissues only. AGC1 deficiency patients are children showing severe hypotonia, arrested psychomotor development, seizures and global hypomyelination. While the effect of AGC1 deficiency in neurons and neuronal function has been deeply studied, little is known about oligodendrocytes and their precursors, the brain cells involved in myelination. Here we studied the effect of AGC1 down-regulation on oligodendrocyte precursor cells (OPCs), using both in vitro and in vivo mouse disease models. In the cell model, we showed that a reduced expression of AGC1 induces a deficit of OPC proliferation leading to their spontaneous and precocious differentiation into oligodendrocytes. Interestingly, this effect seems to be related to a dysregulation in the expression of trophic factors and receptors involved in OPC proliferation/differentiation, such as Platelet-Derived Growth Factor α (PDGFα) and Transforming Growth Factor βs (TGFβs). We also confirmed the OPC reduction in vivo in AGC1-deficent mice, as well as a proliferation deficit in neurospheres from the Subventricular Zone (SVZ) of these animals, thus indicating that AGC1 reduction could affect the proliferation of different brain precursor cells. These data clearly show that AGC1 impairment alters myelination not only by acting on N-acetyl-aspartate production in neurons but also on OPC proliferation and suggest new potential therapeutic targets for the treatment of AGC1 deficiency. View Full-Text
Keywords: mouse model; growth factors; subventricular zone; AGC1 deficiency; mitochondrial disease mouse model; growth factors; subventricular zone; AGC1 deficiency; mitochondrial disease
Show Figures

Figure 1

MDPI and ACS Style

Petralla, S.; Peña-Altamira, L.E.; Poeta, E.; Massenzio, F.; Virgili, M.; Barile, S.N.; Sbano, L.; Profilo, E.; Corricelli, M.; Danese, A.; Giorgi, C.; Ostan, R.; Capri, M.; Pinton, P.; Palmieri, F.; Lasorsa, F.M.; Monti, B. Deficiency of Mitochondrial Aspartate-Glutamate Carrier 1 Leads to Oligodendrocyte Precursor Cell Proliferation Defects Both In Vitro and In Vivo. Int. J. Mol. Sci. 2019, 20, 4486.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop