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AuthorMühling, Tobiasdc.contributor.author
AuthorDuda, Johannadc.contributor.author
AuthorWeishaupt, Jochen H.dc.contributor.author
AuthorLudolph, Albert C.dc.contributor.author
AuthorLiß, Birgitdc.contributor.author
Date of accession2021-10-19T14:21:48Zdc.date.accessioned
Available in OPARU since2021-10-19T14:21:48Zdc.date.available
Date of first publication2014-11-14dc.date.issued
AbstractDisturbances in Ca2+ homeostasis and mitochondrial dysfunction have emerged as major pathogenic features in familial and sporadic forms of Amyotrophic Lateral Sclerosis (ALS), a fatal degenerative motor neuron disease. However, the distinct molecular ALS-pathology remains unclear. Recently, an activity-dependent Ca2+ homeostasis deficit, selectively in highly vulnerable cholinergic motor neurons in the hypoglossal nucleus (hMNs) from a common ALS mouse model, the endstage superoxide dismutase SOD1G93A transgenic mouse, was described. This functional deficit was defined by a reduced hMN mitochondrial Ca2+ uptake capacity and elevated Ca2+ extrusion across the plasma membrane. To address the underlying molecular mechanisms, here we quantified mRNA-levels of respective potential mitochondrial and plasma membrane Ca2+ transporters in individual, choline-acetyltransferase (ChAT) positive hMNs from wildtype (WT) and endstage SOD1G93A mice, by combining UV laser microdissection with RT-qPCR techniques, and specific data normalization. As ChAT cDNA levels as well as cDNA and genomic DNA levels of the mitochondrially encoded NADH dehydrogenase ND1 were not different between hMNs from WT and endstage SOD1G93A mice, these genes were used to normalize hMN-specific mRNA-levels of plasma membrane and mitochondrial Ca2+ transporters, respectively. We detected about 2-fold higher levels of the mitochondrial Ca2+ transporters MCU/MICU1, Letm1, and UCP2 in remaining hMNs from endstage SOD1G93A mice. These higher expression-levels of mitochondrial Ca2+ transporters in individual hMNs were not associated with a respective increase in number of mitochondrial genomes, as evident from hMN specific ND1 DNA quantification. Normalized mRNA-levels for the plasma membrane Na+/Ca2+ exchanger NCX1 were also about 2-fold higher in hMNs from SOD1G93A mice. Thus, pharmacological stimulation of Ca2+ transporters in highly vulnerable hMNs might offer a neuroprotective strategy for ALS.dc.description.abstract
Languageendc.language.iso
PublisherUniversität Ulmdc.publisher
LicenseCC BY 4.0 Internationaldc.rights
Link to license texthttps://creativecommons.org/licenses/by/4.0/dc.rights.uri
KeywordmCUdc.subject
Keywordcholine acetyltransferase ChATdc.subject
KeywordUCP2dc.subject
KeywordLetm1dc.subject
KeywordNCX1dc.subject
KeywordND1dc.subject
KeywordGFAPdc.subject
Dewey Decimal GroupDDC 610 / Medicine & healthdc.subject.ddc
MeSHMitochondria; Pathologydc.subject.mesh
MeSHDNA, Mitochondrialdc.subject.mesh
MeSHCholine O-Acetyltransferasedc.subject.mesh
TitleElevated mRNA-levels of distinct mitochondrial and plasma membrane Ca2+ transporters in individual hypoglossal motor neurons of endstage SOD1 transgenic micedc.title
Resource typeWissenschaftlicher Artikeldc.type
SWORD Date2019-12-19T17:58:32Zdc.date.updated
VersionpublishedVersiondc.description.version
DOIhttp://dx.doi.org/10.18725/OPARU-39123dc.identifier.doi
URNhttp://nbn-resolving.de/urn:nbn:de:bsz:289-oparu-39199-4dc.identifier.urn
GNDMitochondriale DNSdc.subject.gnd
GNDCholin-Acetyltransferasedc.subject.gnd
FacultyMedizinische Fakultätuulm.affiliationGeneral
InstitutionUKU. Klinik für Neurologieuulm.affiliationSpecific
InstitutionInstitut für Angewandte Physiologieuulm.affiliationSpecific
Peer reviewjauulm.peerReview
DCMI TypeCollectionuulm.typeDCMI
CategoryPublikationenuulm.category
DOI of original publication10.3389/fncel.2014.00353dc.relation1.doi
Source - Title of sourceFrontiers in Cellular Neurosciencesource.title
Source - Place of publicationFrontiers Mediasource.publisher
Source - Volume8source.volume
Source - Year2014source.year
Source - Article number353source.articleNumber
Source - eISSN1662-5102source.identifier.eissn
FundingBMBF [NGFN 01GS08134]uulm.funding
FundingAustrian Science Fund [FWF SFB F4412]uulm.funding
FundingAlfried Krupp prizeuulm.funding
FundingGerman network for ALS research (MND-NET)uulm.funding
FundingCharcot Foundation for ALS Researchuulm.funding
FundingVirtual Helmholtz Instituteuulm.funding
Bibliographyuulmuulm.bibliographie
DFG project uulmGRK 1789 / Zelluläre und molekulare Mechanismen der Alterung (CEMMA) / DFG / GRK / 194266605 [LI-1745]uulm.projectDFG


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