Suppression of insult-induced neurogenesis in adult rat brain by brain-derived neurotrophic factor.
In mammals, including humans, the subventricular zone of the lateral ventricle and the subgranular zone of the dentate gyrus contain neural stem cells, which continue to proliferate even in adulthood and give rise to new neurons. Neurogenesis in these areas is enhanced by brain insults. Brain-derived neurotrophic factor (BDNF) promotes neuronal survival and differentiation during the development of the nervous system. In the adult intact brain, BDNF administration in the lateral ventricle or ventricular zone stimulates neurogenesis in several forebrain areas. Here we show that intrahippocampal transduction of recombinant adeno-associated virus carrying the BDNF gene giving rise to levels of BDNF protein sufficient to induce a functional response inhibits the formation of new dentate granule cells triggered by global forebrain ischemia in rats. Our data indicate that long-term delivery of a neurotrophic factor, which is considered as a novel neuroprotective strategy for human brain diseases, may attenuate intrinsic neuroregenerative responses.
Larsson
Elin
E
Section of Restorative Neurology, Wallenberg Neuroscience Center, University Hospital, BMC A-11 SE-221 84, Lund, Sweden.
Mandel
Ronald J
RJ
Klein
Ronald L
RL
Muzyczka
Nicholas
N
Lindvall
Olle
O
Kokaia
Zaal
Z
D000256:Adenoviridae / Q000235:genetics / Q000502:physiology; D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D002545:Brain Ischemia / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D019208:Brain-Derived Neurotrophic Factor / Q000008:administration & dosage* / Q000096:biosynthesis / Q000235:genetics; D002470:Cell Survival / Q000235:genetics / Q000502:physiology; D006131:Growth Inhibitors / Q000008:administration & dosage* / Q000096:biosynthesis / Q000235:genetics; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D008297:Male; D009416:Nerve Regeneration / Q000235:genetics / Q000502:physiology; D009433:Neural Inhibition / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects; D014161:Transduction, Genetic
D019208:Brain-Derived Neurotrophic Factor; D006131:Growth Inhibitors