Casamassa, Antonella (2014) Knocking out the Na+/Ca2+ exchanger NCX3 impairs oligodendrocyte lineage responses and worsens clinical symptoms in experimental autoimmune encephalomyelitis-induced multiple sclerosis in mice. [Tesi di dottorato]

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Item Type: Tesi di dottorato
Resource language: English
Title: Knocking out the Na+/Ca2+ exchanger NCX3 impairs oligodendrocyte lineage responses and worsens clinical symptoms in experimental autoimmune encephalomyelitis-induced multiple sclerosis in mice
Creators:
CreatorsEmail
Casamassa, Antonellaantonellacasamassa@gmail.com
Date: 28 March 2014
Number of Pages: 106
Institution: Università degli Studi di Napoli Federico II
Department: Neuroscienze e Scienze Riproduttive ed Odontostomatologiche
Scuola di dottorato: Medicina molecolare
Dottorato: Neuroscienze
Ciclo di dottorato: 26
Coordinatore del Corso di dottorato:
nomeemail
Annunziato, Luciolannunzi@unina.it
Tutor:
nomeemail
Annunziato, LucioUNSPECIFIED
Date: 28 March 2014
Number of Pages: 106
Keywords: EAE; multiple sclerosis; Na+/Ca2+ exchanger
Settori scientifico-disciplinari del MIUR: Area 05 - Scienze biologiche > BIO/14 - Farmacologia
Area 06 - Scienze mediche > MED/26 - Neurologia
Date Deposited: 09 Apr 2014 08:24
Last Modified: 08 May 2017 01:00
URI: http://www.fedoa.unina.it/id/eprint/9712

Collection description

Abstract The dysregulation of [Ca2+]i and [Na+]i homeostasis is involved in neuronal and glial response occurring in several neurodegenerative diseases, including Multiple Sclerosis. The Na+/Ca2+ exchanger can be considered a key player in modulating the [Ca2+]i and [Na+]i homeostasis following the injury. Recent evidence point out to the isoform NCX3 of the Na+/Ca2+ exchanger as a new potential therapeutic target for neuroprotection. The aim of the present study was to establish the role played by NCX3 in a murine model of Multiple Sclerosis. The experimental model used in these studies was the Experimental Autoimmune Encephalomyelitis (EAE). Biochemical analysis performed on spinal cord tissue homogenates revealed that NCX3 protein levels were progressively up-regulated during EAE progression; this effect was more significant at EAE chronic stage. In addition, quantitative confocal double immunofluorescence experiments showed that the co-expression of NCX3 with both the myelin marker myelin basic protein (MBP) and the axonal marker neurofilament 200 (NF200) was significantly down-regulated at peak and chronic stages of EAE disease. By contrast, quantification of co-localization studies revealed that the co-expression of NCX3 with the oligodendrocyte lineage markers, the membrane chondroitin sulfate proteoglycan NG2, the Galactocebroside (GalC), and the 2’-3’-cyclic nucleotide-3’-phosphodiesterase (CNPase) was up-regulated during EAE progression. Interestingly, this up-regulation was more significant at EAE chronic stage. These early results suggested that NCX3 isoform might be involved in neuroprotective responses mediated by oligodendrocytes during the EAE recovery phase. The importance of the NCX3 isoform in oligodendroglial responses following EAE insult was supported by several findings: 1) at chronic stage of EAE disease, NCX3 knockout (ncx3-/-) mice displayed a reduced number of NG2 and CNPase positive cells when compared to NCX3 congenic wild type (ncx3+/+) mice; 2) NCX3 knockout (ncx3-/-) mice showed an earlier onset of symptoms and an increased susceptibility to the EAE disease when compared to NCX3 congenic wild type (ncx3+/+) mice. In conclusion, our findings suggested that NCX3 exchanger, by modulating [Na+]i and [Ca2+]i homeostasis might play an important role in controlling oligodendrocyte response after a demyelinating insult.

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