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Neurogenesis in the adult olfactory bulb
Olfactory bulb
Rostralmigratorystream
Dentate gyrus
C cell Progenitor cell division(Expansion)
B cell “Stem cell” division
A cell
At least two types of newinterneurons in the granularand periglomerular layer
Type-1 Type-3Type-2
Migration(”chain migration”)
Differentiation(neurite extension),selection andsurvival, maturation
Neurogenesis in the adult hippocampus
Progenitorcell division(Expansion)
Migration,Exit fromcell cycle
“Stem cell” division
Newgranule
cells
to CA3
Period of lowthreshold forLTP inductionand highexcitability
Lasting synapticinput (glutamatergic,
excitatory)First synapticinput (tonic,GABAergic,excitatory)
Differentiation(neurite extension),selectionand survival,maturation
Simplified sequence of marker expression
GFAP
BLBP
Nestin, Sox2
DCX, PSA-NCAM
Calretinin, Tuc4 Calbindin
NeuN
Simplified sequence of marker expression
New neuron
GFAP EGFR, Dlx
BLBP, (Pax6) DCX, PSA-NCAM, Ascl1 Calretinin, (TH)
Nestin, Sox2 NeuN
Note: not all marker combinations are present in all cells.
Oligodendrocytic lineage
PDGFRα Olig2
Adult neurogenesis
Suggested readings (recent Review articles only):
Duan X, Kang E, Liu CY, Ming GL, Song H. Development of neural stemcell in the adult brain. Curr Opin Neurobiol. 2008 Feb;18(1):108-15. Epub2008 May 29. Review. PMID: 18514504
Ehninger D, Kempermann G. Neurogenesis in the adult hippocampus. CellTissue Res. 2008; 331(1):243-50. PMID: 17938969
Eisch AJ, Cameron HA, Encinas JM, Meltzer LA, Ming GL, Overstreet-Wadiche LS. Adult neurogenesis, mental health, and mental illness: hopeor hype? J Neurosci. 2008 12; 28(46):11785-91. PMID: 19005040
Fabel K, Kempermann G. Physical activity and the regulation ofneurogenesis in the adult and aging brain. Neuromolecular Med. 2008;10(2):59-66. PMID: 18286387
Gould E. How widespread is adult neurogenesis in mammals? Nat RevNeurosci. 2007; 8(6):481-8. PMID: 17514200
Ihrie RA, Alvarez-Buylla A. Cells in the astroglial lineage are neural stemcells. Cell Tissue Res. 2008; 331(1):179-91. PMID: 17786483
Kempermann G. The neurogenic reserve hypothesis: what is adulthippocampal neurogenesis good for? Trends Neurosci. 2008; 31(4):163-9.PMID: 18329110
Lledo PM, Merkle FT, Alvarez-Buylla A. Origin and function of olfactorybulb interneuron diversity. Trends Neurosci. 2008; 31(8):392-400. PMID:18603310
Lledo PM, Alonso M, Grubb MS. Adult neurogenesis and functional plasticityin neuronal circuits. Nat Rev Neurosci. 2006; 7(3):179-93. PMID: 16495940
Parent JM, Murphy GG. Mechanisms and functional significance ofaberrant seizure-induced hippocampal neurogenesis. Epilepsia. 2008;49Suppl 5:19-25. PMID: 18522597
Sahay A, Hen R. Adult hippocampal neurogenesis in depression. NatNeurosci. 2007; 10(9):1110-5. PMID: 17726477
Zhao C, Deng W, Gage FH. Mechanisms and functional implications ofadult neurogenesis. Cell. 2008; 132(4):645-60. PMID: 18295581
www.abcam.com
By Gerd Kempermann*and Abcam
Copyright © 2009 Abcam, All Rights Reserved. The Abcam logo is a registered trademark. All information/detail is correct at time of going to print.
Abcam:Leading provider of primary and secondaryantibodies to researchers worldwide. Abcam'scatalogue of over 50,000 reagents includescutting edge tools for neuroscience, chromatin,stem cells, immunology, cancer, cardiovascularand nuclear signalling research. We have over13,000 products in the Neuroscience field thatinclude antibodies, proteins and lysates.
We have 1,380 products for neurogenesis.These include:
• ALDH1A1 antibody (ab23375)• Ascl1 antibody (ab38557)• BLBP antibody (ab32423)• Calretinin antibody (ab3934)• Doublecortin antibody (ab18723)• Dlx2 antibody (ab18188)• EGFR antibody (ab2430)• GFAP antibody (ab7260)• Nestin antibody (ab5968)• NeuroD1 (ab16508)• Olig2 antibody (ab33427)• Prox1 antibody (ab11941)• PAX6 antibody (ab5790)• PDGFR alpha antibody (ab61219)• Sox2 antibody (ab15830)• Sox9 antibody (ab3697)• Tuc4 antibody (ab23851)
• And many more at: www.abcam.com
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The author*Gerd Kempermann, born 1965, has been working on adulthippocampal neurogenesis since 1995. His main interestsare the activity-dependent control of adult neurogenesis,the genetic complexity underlying this control, and thefunctional contribution of the newborn neurons to thehippocampal network. He is Professor for Genomics ofRegeneration at the CRTD - the DFG Research Center forRegenerative Therapies Dresden, Germany.The author would like to thank Sebastian Jessberger forcomments on the draft of this poster.
The bookGerd Kempermann haspublished a monographon “Adult Neurogenesis -Stem cells and neuronaldevelopment in the adultbrain” (Oxford UniversityPress, New York 2006,ISBN 0-19-517971-4)that gives a introductionto the general conceptsof the field as well as adetailed overview aboutthe current knowledgeabout new neurons inthe adult brain.
Adult neurogenesis• is the development of new functioning neurons in the adult brain• occurs in two neurogenic regions in the dentate gyrus of the
hippocampus and the olfactory bulb• originates from precursor cells in the subgranular zone (SGZ) in
the dentate gyrus and the subventricular zone (SVZ) of the lateralventricles
• has been described for all mammalian species investigated,including non-human primates and humans
• might also occur outside the two neurogenic regions (1) inabortive form (i.e. to the level of the expression of immatureneuronal markers), (2) in reaction to damage and ischemia, and(3) at very low physiological levels, but available data are oftenconflicting and no complete coherent picture has emerged yet.
• was discovered in the 1960s by Josef Altman but attractedwidespread interest only from the 1990s onwards, when the linkto neural stem cell biology had become apparent
Neural precursor cells• from the neurogenic regions show stem cell properties (self-
renewal and multipotency) when put into cell culture but usuallyshow a more limited potential in vivo
• reside within a neurogenic niche resembling other stem cellniches in the body, e.g. in bone marrow or testes
• have glial features and properties of radial glia• express characteristic markers such as Nestin or Sox2, but no specific
markers have been found that would allow prospective isolation• from the two neurogenic regions show different properties ex
vivo but the few available cross-transplantation experimentssuggest a major impact of the niche on the actual differentiationpotential
Regulation of Adult neurogenesis• decreases with age but appears to remain present at low levels
even at oldest age
• is regulated in response to behavioral stimuli, including physicalactivity, exposure to complexity, and learning
• is controlled at different stages of neuronal development:proliferation of precursor cells, survival, migration, maturationand functional synaptic integration
• is a polygenic trait with large natural variation
Molecular bases of adult neurogenesis• Many genes with relevance for cortical neurogenesis in the
embryo are also involved in adult neurogenesis: Pax6,Neurogenin2, Mash1 (Ascl1), NeuroD1
• Molecular details differ between the two neurogenic regionsreflecting the different lineages of new neurons: glutamatergicprincipal neurons (granule cells) in the dentate gyrus and (atleast) two types of interneurons in the olfactory bulb. Prox1, forexample, is only expressed in the SGZ; Olig2 almost exclusivelyin the SVZ
FunctionNew neurons in the adult hippocampus• might contribute to optimizing the strength of the highly plastic
mossy fiber connection between the dentate gyrus and areaCA3 and are thus exerting a function at a bottleneck in thehippocampal network
• have been linked to the processing of information in the sense offorming temporal associations and integrating information into contexts
• also play a role in affective behavior, underscoring the linkbetween cognition and emotion in the hippocampus
New neurons in the adult olfactory bulb• have been linked to the maintenance of network integrity in the
face of the high turnover rate of receptor neurons in the olfactoryepithelium and contribute to the variety of olfactory interneurons
• show increased sensitivity to novel odors, including pheromones• might be involved in the formation of olfactory memories
Medical relevanceAdult neurogenesis in the hippocampus• has been brought into connection with the pathogenesis of
particular (cognitive aspects of) dementias, major depressionand schizophrenia
• might be relevant for explaining cognitive impairment in agingdue to decreasing plasticity
• might be impaired in the context of various conditions,explaining hippocampus-dependent cognitive symptoms (e.g.infection, diabetes,
Adult neurogenesis in the olfactory bulb• might be impaired in the context of various conditions, explaining
symptoms related to olfaction (e.g. in Parkinson and AlzheimerDisease)
• might provide precursor cells attracted to the site of pathology,e.g. after a stroke in the striatum
Note: The goal of this poster is to provide a very first overview onadult neurogenesis and summarize a few key facts in a simplifiedway. No misinterpretation of the work of others was intended.
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