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Deficiency in Endothelin Receptor B Reduces Proliferation of Neuronal Progenitors and Increases Apoptosis in Postnatal Rat Cerebellum

Vidovic, Maria; Chen, Ming-Ming; Lu, Qun-Ying; Kalloniatis, Katherine; Martin, Ben; Tan, Abel; Lynch, Celina; Croaker, David; Cass, Daniel; Song, Zan-Min

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Endothelins regulate cellular functions in the mammalian brain through the endothelin receptors A and B (EDNRA and EDNRB). In this study, we investigated the role of EDNRB on cell proliferation in the cerebellum by using the spotting lethal (sl) rat, which carries a naturally occurring deletion in the EDNRB gene. Proliferating cells in the three genotypes, wild-type (+/+), heterozygous (+/sl) and homozygous mutant (sl/sl) rats were labelled by intraperitoneal injection of...[Show more]

dc.contributor.authorVidovic, Maria
dc.contributor.authorChen, Ming-Ming
dc.contributor.authorLu, Qun-Ying
dc.contributor.authorKalloniatis, Katherine
dc.contributor.authorMartin, Ben
dc.contributor.authorTan, Abel
dc.contributor.authorLynch, Celina
dc.contributor.authorCroaker, David
dc.contributor.authorCass, Daniel
dc.contributor.authorSong, Zan-Min
dc.date.accessioned2015-12-08T22:26:39Z
dc.identifier.issn0272-4340
dc.identifier.urihttp://hdl.handle.net/1885/33722
dc.description.abstractEndothelins regulate cellular functions in the mammalian brain through the endothelin receptors A and B (EDNRA and EDNRB). In this study, we investigated the role of EDNRB on cell proliferation in the cerebellum by using the spotting lethal (sl) rat, which carries a naturally occurring deletion in the EDNRB gene. Proliferating cells in the three genotypes, wild-type (+/+), heterozygous (+/sl) and homozygous mutant (sl/sl) rats were labelled by intraperitoneal injection of 5-bromo-2′-deoxyuridine (BrdU) at postnatal day 2. The density of BrdU-positive cells (per mm2) in the external germinal layer of sl/sl rats (Mean ± SEM, 977 ± 388) was significantly reduced compared to +/+ (4915 ± 631) and +/sl (2304 ± 557) rats. Subsequently, we examined the effects of EDNRB mutation on neural apoptosis by terminal deoxynucleotidyltransferase-mediated dUTP nick end-labelling assay. This showed that the density of apoptotic cells in the cerebella of sl/sl rats (9.3 ± 0.5/mm2) was significantly more increased than +/+ rats (4 ± 0.7). The expression of brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) were measured with standard ELISA, but were unchanged in all genotypes. These results suggest that ENDRB mediates neural proliferation and have anti-apoptotic effects in the cerebellum of the postnatal rat, and that these effects are independent of changes in the expression of BDNF and GDNF. Our findings will lead to better understanding of the morphological changes in the cerebellum of Hirschsprung's disease patients with congenital EDNRB mutation.
dc.publisherKluwer Academic Publishers
dc.sourceCellular and Molecular Neurobiology
dc.subjectKeywords: brain derived neurotrophic factor; broxuridine; endothelin B receptor; glial cell line derived neurotrophic factor; animal experiment; apoptosis; article; cell proliferation; cerebellum; controlled study; enzyme linked immunosorbent assay; gene deletion; 5-bromo-2'-deoxyuridine; Apoptotic cells; Cerebellum; Development; Endothelin system; Hirschsprung disease; Spotting lethal rat
dc.titleDeficiency in Endothelin Receptor B Reduces Proliferation of Neuronal Progenitors and Increases Apoptosis in Postnatal Rat Cerebellum
dc.typeJournal article
local.description.notesImported from ARIES
local.identifier.citationvolume28
dc.date.issued2008
local.identifier.absfor060104 - Cell Metabolism
local.identifier.ariespublicationu4241283xPUB105
local.type.statusPublished Version
local.contributor.affiliationVidovic, Maria, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationChen, Ming-Ming, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationLu, Qun-Ying, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationKalloniatis, Katherine, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationMartin, Ben, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationTan, Abel, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationLynch, Celina, The Canberra Hospital
local.contributor.affiliationCroaker, David, Canberra Hospital
local.contributor.affiliationCass, Daniel, Royal Alexandra Hospital for Children
local.contributor.affiliationSong, Zan-Min, College of Medicine, Biology and Environment, ANU
local.description.embargo2037-12-31
local.bibliographicCitation.issue8
local.bibliographicCitation.startpage1129
local.bibliographicCitation.lastpage1138
local.identifier.doi10.1007/s10571-008-9292-z
dc.date.updated2016-02-24T10:47:11Z
local.identifier.scopusID2-s2.0-57449108746
local.identifier.thomsonID000261329500010
CollectionsANU Research Publications

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