Endothelin b receptor deficiency is associated with an increased rate of neuronal apoptosis in the dentate gyrus.
The dentate gyrus retains neuronal proliferative potential throughout life. Using immature endothelin B receptor-deficient (sl/sl) rats, a rabbit model of pneumococcal meningitis and autopsy brains from humans who died from pneumococcal meningitis, we explored the role of endothelin B receptors in physiological and pathological neuronal apoptosis in the dentate gyrus. At postnatal days 3-4, the rate of apoptosis in the dentate gyrus was high in all rats, declining to low levels in wild-type rats (+/+) on days 14 and 22, but remaining high in both homozygous (sl/sl) and heterozygous (sl/+) endothelin B receptor-deficient rats. Increased apoptosis was not significantly compensated for by neuronal proliferation. Hippocampal neuronal cultures also exhibited genotype-dependent apoptosis with the highest rate in neurons from homozygous endothelin B receptor-deficient (sl/sl) rats. In rabbit and human pneumococcal meningitis, increased apoptosis in the dentate gyrus was associated with loss of neuronal endothelin B receptor immunoreactivity. In conclusion, endothelin B receptors appear to act as neuronal survival factors in the dentate gyrus in rodents and man, both during postnatal development and under pathological conditions.
Ehrenreich
H
H
Max-Planck-Institute for Experimental Medicine and Department of Neurology, Göttingen, Germany. ehrenreich@exmax1.mpiem.gwdg.de
Nau
T R
TR
Dembowski
C
C
Hasselblatt
M
M
Barth
M
M
Hahn
A
A
Schilling
L
L
Sirén A-L
Brück
W
W
D000375:Aging / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000378:metabolism / Q000502:physiology; D017209:Apoptosis; D002455:Cell Division; D002478:Cells, Cultured; D018891:Dentate Gyrus / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008586:Meningitis, Pneumococcal / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000502:physiology*; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000172:deficiency*
D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin