机构:[1]Division of Neuroscience, John Curtin School of Medical Research, Australian National University, Building 54, Garran Road, Canberra, ACT 0200, Australia[2]Medical School, Australian National University, Canberra, ACT, Australia[3]Paediatric Surgery, The Canberra Hospital, Canberra, ACT, Australia[4]Children’s Hospital at Westmead, Sydney, NSW, Australia[5]Department of Gynecology and Obstetrics, the First Affiliated Hospital, Kunming Medical College, Yunan, China外科科室妇产科产科妇科昆明医科大学附属第一医院
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 BrdUpositive 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 brainderived 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.
基金:
Canberra Hospital Private Practice Fund; ACT Government
第一作者机构:[1]Division of Neuroscience, John Curtin School of Medical Research, Australian National University, Building 54, Garran Road, Canberra, ACT 0200, Australia
通讯作者:
推荐引用方式(GB/T 7714):
Vidovic Maria,Chen Ming-Ming,Lu Qun-Ying,et al.Deficiency in Endothelin Receptor B Reduces Proliferation of Neuronal Progenitors and Increases Apoptosis in Postnatal Rat Cerebellum[J].CELLULAR AND MOLECULAR NEUROBIOLOGY.2008,28(8):1129-1138.doi:10.1007/s10571-008-9292-z.
APA:
Vidovic, Maria,Chen, Ming-Ming,Lu, Qun-Ying,Kalloniatis, Katherine F.,Martin, Ben M....&Song, Zan-Min.(2008).Deficiency in Endothelin Receptor B Reduces Proliferation of Neuronal Progenitors and Increases Apoptosis in Postnatal Rat Cerebellum.CELLULAR AND MOLECULAR NEUROBIOLOGY,28,(8)
MLA:
Vidovic, Maria,et al."Deficiency in Endothelin Receptor B Reduces Proliferation of Neuronal Progenitors and Increases Apoptosis in Postnatal Rat Cerebellum".CELLULAR AND MOLECULAR NEUROBIOLOGY 28..8(2008):1129-1138