Telomerase activity in the subventricular zone of adult mice.
The subventricular zone (SVZ) is the most active site for the production of new neurons in the adult mouse brain. Neural stem cells in the adult SVZ give rise to neuroblasts that travel via the rostral migratory stream (RMS) to the olfactory bulb, where they differentiate into interneurons. The enzyme telomerase has been identified in other population of stem cells and is necessary for the synthesis of telomeric DNA to prevent chromosomal shortening, end-to-end fusions, and apoptosis during successive rounds of cell division. However, previous studies have failed to detect telomerase in the adult mammalian brain. Here we demonstrate that telomerase is expressed by all brain regions shortly after birth, but becomes restricted to the SVZ and olfactory bulb in the adult mouse brain. Cultures of neural precursor cells or of migratory neuroblasts purified from the SVZ were each found to possess telomerase activity. After elimination of migrating neuroblasts and immature precursor cells in vivo by treatment with cytosine-beta-D-arabinofuranoside (Ara-C), telomerase activity was still detectable in the remaining SVZ, which includes a population of neural stem cells. Following withdrawal of Ara-C, telomerase activity subsequently increased with a time course that parallels regeneration of the SVZ network and RMS. Finally, intracranial surgery alone, which has previously been shown to increase the number of cells in the SVZ, produced higher telomerase levels in the SVZ. We conclude that telomerase is active in neural precursor cells of the adult mouse and suggest that its regulation is an important parameter for cellular proliferation to occur in the mammalian brain.
Caporaso
Gregg L
GL
Molecular Neurobiology Program, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA. caporaso@saturn.med.nyu.edu
Lim
Daniel A
DA
Alvarez-Buylla
Arturo
A
Chao
Moses V
MV
D000375:Aging / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003561:Cytarabine / Q000494:pharmacology; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000201:enzymology*; D009830:Olfactory Bulb / Q000166:cytology / Q000201:enzymology* / Q000254:growth & development*; D013234:Stem Cells / Q000166:cytology / Q000201:enzymology*; D013687:Telencephalon / Q000166:cytology / Q000201:enzymology* / Q000254:growth & development*; D019098:Telomerase / Q000037:antagonists & inhibitors / Q000378:metabolism*
D003561:Cytarabine; D019098:Telomerase