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Variant Brain-Derived Neurotrophic Factor (Val66Met) Alters Adult Olfactory Bulb Neurogenesis and Spontaneous Olfactory Discrimination
- Source :
- Journal of Neuroscience, Journal of Neuroscience, Society for Neuroscience, 2008, 28 (10), pp.2383-2393. ⟨10.1523/JNEUROSCI.4387-07.2008⟩
- Publication Year :
- 2008
-
Abstract
- Neurogenesis, the division, migration, and differentiation of new neurons, occurs throughout life. Brain derived neurotrophic factor (BDNF) has been identified as a potential signaling molecule regulating neurogenesis in the subventricular zone (SVZ), but its functional consequencesin vivohave not been well defined. We report marked and unexpected deficits in survival but not proliferation of newly born cells of adult knock-in mice containing a variant form of BDNF [a valine (Val) to methionine (Met) substitution at position 66 in the prodomain of BDNF (Val66Met)], a genetic mutation shown to lead to a selective impairment in activity-dependent BDNF secretion. Utilizing knock-out mouse lines, we identified BDNF and tyrosine receptor kinase B (TrkB) as the critical molecules for the observed impairments in neurogenesis, with p75 knock-out mice showing no effect on cell proliferation or survival. We then localized the activated form of TrkB to a discrete population of cells, type A migrating neuroblasts, and demonstrate a decrease in TrkB phosphorylation in the SVZ of Val66Met mutant mice. With these findings, we identify TrkB signaling, potentially through activity dependent release of BDNF, as a critical step in the survival of migrating neuroblasts. Utilizing a behavioral task shown to be sensitive to disruptions in olfactory bulb neurogenesis, we identified specific impairments in spontaneous olfactory discrimination, but not general olfactory sensitivity or habituation to olfactory stimuli in BDNF mutant mice. Through these observations, we have identified novel links between genetic variant BDNF and adult neurogenesisin vivo, which may contribute to significant impairments in olfactory function.
- Subjects :
- Olfactory system
Male
Cell Survival
[SDV]Life Sciences [q-bio]
Subventricular zone
Tropomyosin receptor kinase B
Olfaction
Biology
Article
Discrimination Learning
03 medical and health sciences
Mice
0302 clinical medicine
Methionine
Neuroblast
Cell Movement
medicine
Animals
Receptor, trkB
10. No inequality
ComputingMilieux_MISCELLANEOUS
Cells, Cultured
030304 developmental biology
Cell Proliferation
Brain-derived neurotrophic factor
Mice, Knockout
0303 health sciences
General Neuroscience
Brain-Derived Neurotrophic Factor
Stem Cells
Neurogenesis
Genetic Variation
Valine
Olfactory Pathways
Olfactory Bulb
Olfactory bulb
Protein Structure, Tertiary
Mice, Inbred C57BL
medicine.anatomical_structure
nervous system
Amino Acid Substitution
[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
Neuroscience
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 02706474 and 15292401
- Database :
- OpenAIRE
- Journal :
- Journal of Neuroscience, Journal of Neuroscience, Society for Neuroscience, 2008, 28 (10), pp.2383-2393. ⟨10.1523/JNEUROSCI.4387-07.2008⟩
- Accession number :
- edsair.doi.dedup.....4d8d272bfc09d42973ec8af69c7979c0