Dynamics of olfactory and hippocampal neurogenesis in adult sheep.
Although adult neurogenesis has been conserved in higher vertebrates such as primates and humans, timing of generation, migration, and differentiation of new neurons appears to differ from that in rodents. Sheep could represent an alternative model to studying neurogenesis in primates because they possess a brain as large as a macaque monkey and have a similar life span. By using a marker of cell division, bromodeoxyuridine (BrdU), in combination with several markers, the maturation time of newborn cells in the dentate gyrus (DG) and the main olfactory bulb (MOB) was determined in sheep. In addition, to establish the origin of adult-born neurons in the MOB, an adeno-associated virus that infects neural cells in the ovine brain was injected into the subventricular zone (SVZ). A migratory stream was indicated from the SVZ up to the MOB, consisting of neuroblasts that formed chain-like structures. Results also showed a long neuronal maturation time in both the DG and the MOB, similar to that in primates. The first new neurons were observed at 1 month in the DG and at 3 months in the MOB after BrdU injections. Thus, maturation of adult-born cells in both the DG and the MOB is much longer than that in rodents and resembles that in nonhuman primates. This study points out the importance of studying the features of adult neurogenesis in models other than rodents, especially for translational research for human cellular therapy.
INRA, Unité Mixte de Recherche 85 Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France.
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Brus
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Meurisse
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Gheusi
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Keller
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Lledo
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Lévy
D053687:Adult Stem Cells / Q000502:physiology; D000367:Age Factors; D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count; D002454:Cell Differentiation; D002465:Cell Movement; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics; D006624:Hippocampus / Q000166:cytology*; D006801:Humans; D020547:Lateral Ventricles / Q000166:cytology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D055495:Neurogenesis / Q000502:physiology*; D009830:Olfactory Bulb / Q000166:cytology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D012756:Sheep / Q000033:anatomy & histology*; D014161:Transduction, Genetic
D009419:Nerve Tissue Proteins; D016760:Proto-Oncogene Proteins c-fos; D055748:SOXB1 Transcription Factors; D049452:Green Fluorescent Proteins; D001973:Bromodeoxyuridine