1
Neurogenesis in the adult olfactory bulb Olfactory bulb Rostral migratory stream Dentate gyrus C cell Progenitor cell division (Expansion) B cell “Stem cell” division A cell At least two types of new interneurons in the granular and periglomerular layer Type-1 Type-3 Type-2 Migration (”chain migration”) Differentiation (neurite extension), selection and survival, maturation Neurogenesis in the adult hippocampus Progenitor cell division (Expansion) Migration, Exit from cell cycle “Stem cell” division New granule cells to CA3 Period of low threshold for LTP induction and high excitability Lasting synaptic input (glutamatergic, excitatory) First synaptic input (tonic, GABAergic, excitatory) Differentiation (neurite extension), selection and 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 neuro g enesis Suggested readings (recent Review articles only): Duan X, Kang E, Liu CY , Ming GL, Song H. Development of neural stem cell in the adult brain. Curr Opin Neurobiol. 2008 Feb;18(1):108-15. Epub 2008 May 29. Review . PMID: 18514504 Ehninger D, Kempermann G. Neurogenesis in the adult hippocampus. Cell Tissue 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: hope or hype? J Neurosci. 2008 12; 28(46):11785-91. PMID: 19005040 Fabel K, Kempermann G. Physical activity and the regulation of neurogenesis 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 Rev Neurosci. 2007; 8(6):481-8. PMID: 17514200 Ihrie RA, Alvarez-Buylla A. Cells in the astroglial lineage are neural stem cells. Cell Tissue Res. 2008; 331(1):179-91. PMID: 17786483 Kempermann G. The neurogenic reserve hypothesis: what is adult hippocampal neurogenesis good for? Trends Neurosci. 2008; 31(4):163-9. PMID: 18329110 Lledo PM, Merkle FT, Alvarez-Buylla A. Origin and function of olfactory bulb interneuron diversity . Trends Neurosci. 2008; 31(8):392-400. PMID: 18603310 Lledo PM, Alonso M, Grubb MS. Adult neurogenesis and functional plasticity in neuronal circuits. Nat Rev Neurosci. 2006;7(3):179-93. PMID: 16495940 Parent JM, Murphy GG. Mechanisms and functional significance of aberrant seizure-induced hippocampal neurogenesis. Epilepsia. 2008;49 Suppl 5:19-25. PMID: 18522597 Sahay A, Hen R. Adult hippocampal neurogenesis in depression. Nat Neurosci. 2007; 10(9):1110-5. PMID: 17726477 Zhao C, Deng W , Gage FH. Mechanisms and functional implications of adult 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 secondary antibodies to researchers worldwide. Abcam's catalogue of over 50,000 reagents includes cutting edge tools for neuroscience, chromatin, stem cells, immunology, cancer, cardiovascular and nuclear signalling research.We have over 13,000 products in the Neuroscience field that include 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 Doublecortin antibody (ab18723) BLBP antibody (ab32423) GFAP antibody (ab7260) Dlx2 antibody (ab18188) Sox2 antibody (ab15830) Related antibodies The author* Gerd Kempermann, born 1965, has been working on adult hippocampal neurogenesis since 1995. His main interests are the activity-dependent control of adult neurogenesis, the genetic complexity underlying this control, and the functional contribution of the newborn neurons to the hippocampal network. He is Professor for Genomics of Regeneration at the CRTD - the DFG Research Center for Regenerative Therapies Dresden, Germany . The author would like to thank Sebastian Jessberger for comments on the draft of this poster . The book Gerd Kempermann has published a monograph on Adult Neurogenesis - Stem cells and neuronal development in the adult brain” (Oxford University Press, New Y ork 2006, ISBN 0-19-517971-4) that gives a introduction to the general concepts of the field as well as a detailed overview about the current knowledge about new neurons in the 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 lateral ventricles has been described for all mammalian species investigated, including non-human primates and humans might also occur outside the two neurogenic regions (1) in abortive form (i.e. to the level of the expression of immature neuronal markers), (2) in reaction to damage and ischemia, and (3) at very low physiological levels, but available data are often conflicting and no complete coherent picture has emerged yet. was discovered in the 1960s by Josef Altman but attracted widespread interest only from the 1990s onwards, when the link to 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 usually show a more limited potential in vivo reside within a neurogenic niche resembling other stem cell niches in the body, e.g. in bone marrow or testes have glial features and properties of radial glia express characteristic mark ers such as Nestin or Sox2, but no specific mark ers have been found that would allow prospective isolation from the two neurogenic regions show different properties ex vivo but the few available cross-transplantation experiments suggest a major impact of the niche on the actual differentiation potential 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 physical activity, exposure to complexity, and learning is controlled at different stages of neuronal development: proliferation of precursor cells, survival, migration, maturation and 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 regions reflecting the different lineages of new neurons: glutamatergic principal neurons (granule cells) in the dentate gyrus and (at least) two types of interneurons in the olfactory bulb . Prox1, for example, is only expressed in the SGZ; Olig2 almost exclusively in the SVZ Function New neurons in the adult hippocampus might contribute to optimizing the strength of the highly plastic mossy fiber connection between the dentate gyrus and area CA3 and are thus exerting a function at a bottleneck in the hippocampal network have been link ed to the processing of information in the sense of forming temporal associations and integrating information into contexts also play a role in affective behavior, underscoring the link between cognition and emotion in the hippocampus New neurons in the adult olfactory bulb have been link ed to the maintenance of network integrity in the face of the high turnover rate of receptor neurons in the olfactory epithelium 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 relevance Adult neurogenesis in the hippocampus has been brought into connection with the pathogenesis of particular (cognitive aspects of) dementias, major depression and schizophrenia might be relevant for explaining cognitive impairment in aging due 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 Alzheimer Disease) 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 on adult neurogenesis and summarize a few key facts in a simplified way . No misinterpretation of the work of others was intended. Enter our iPod competition and view more neurogenesis pathways visit at: www.abcam.com/neurogenesiscomp

Adult neurogenesis AbcamNeurogenesis in the adult hippocampus Progenitor cell division (Expansion) Migration, Exit from cell cycle “Stem cell” division New granule cells to CA3

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Page 1: Adult neurogenesis AbcamNeurogenesis in the adult hippocampus Progenitor cell division (Expansion) Migration, Exit from cell cycle “Stem cell” division New granule cells to CA3

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

Doublecortin antibody(ab18723)

BLBP antibody(ab32423)

GFAP antibody(ab7260)

Dlx2 antibody(ab18188)

Sox2 antibody(ab15830)

Related antibodies

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.

Enter our iPod competitionand view more neurogenesispathways visit at:

www.abcam.com/neurogenesiscomp