PMID- 18683040
OWN - NLM
STAT- MEDLINE
DCOM- 20090320
LR  - 20211020
IS  - 1573-6830 (Electronic)
IS  - 0272-4340 (Linking)
VI  - 28
IP  - 8
DP  - 2008 Dec
TI  - Deficiency in endothelin receptor B reduces proliferation of neuronal progenitors 
      and increases apoptosis in postnatal rat cerebellum.
PG  - 1129-38
LID - 10.1007/s10571-008-9292-z [doi]
AB  - 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 
      5-bromo-2'-deoxyuridine (BrdU) at postnatal day 2. The density of BrdU-positive 
      cells (per mm(2)) 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/mm(2)) 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.
FAU - Vidovic, Maria
AU  - Vidovic M
AD  - Division of Neuroscience, John Curtin School of Medical Research, Australian 
      National University, Canberra, ACT 0200, Australia.
FAU - Chen, Ming-Ming
AU  - Chen MM
FAU - Lu, Qun-Ying
AU  - Lu QY
FAU - Kalloniatis, Katherine F
AU  - Kalloniatis KF
FAU - Martin, Ben M
AU  - Martin BM
FAU - Tan, Abel H Y
AU  - Tan AH
FAU - Lynch, Celina
AU  - Lynch C
FAU - Croaker, G David H
AU  - Croaker GD
FAU - Cass, Daniel T
AU  - Cass DT
FAU - Song, Zan-Min
AU  - Song ZM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080806
PL  - United States
TA  - Cell Mol Neurobiol
JT  - Cellular and molecular neurobiology
JID - 8200709
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Glial Cell Line-Derived Neurotrophic Factor)
RN  - 0 (Receptor, Endothelin B)
RN  - G34N38R2N1 (Bromodeoxyuridine)
SB  - IM
MH  - Animals
MH  - *Apoptosis
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Bromodeoxyuridine/metabolism
MH  - Cell Count
MH  - Cell Nucleus/metabolism
MH  - Cell Proliferation
MH  - Cerebellum/*cytology/*metabolism
MH  - Glial Cell Line-Derived Neurotrophic Factor/metabolism
MH  - In Situ Nick-End Labeling
MH  - Mutation/genetics
MH  - Neurons/*cytology/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Receptor, Endothelin B/*deficiency/metabolism
MH  - Stem Cells/*cytology/metabolism
EDAT- 2008/08/07 09:00
MHDA- 2009/03/21 09:00
CRDT- 2008/08/07 09:00
PHST- 2007/12/20 00:00 [received]
PHST- 2008/06/17 00:00 [accepted]
PHST- 2008/08/07 09:00 [pubmed]
PHST- 2009/03/21 09:00 [medline]
PHST- 2008/08/07 09:00 [entrez]
AID - 10.1007/s10571-008-9292-z [doi]
PST - ppublish
SO  - Cell Mol Neurobiol. 2008 Dec;28(8):1129-38. doi: 10.1007/s10571-008-9292-z. Epub 
      2008 Aug 6.