Home LiteratureArticle Details
PMID: 11978843 Published · ppublish English Journal Article Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Regulation of neurogenesis in adult mouse hippocampus by cAMP and the cAMP response element-binding protein.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 22 ·No. 9 ·2002-05-01 ·Pages 3673-82

Nakagawa S, Kim JE, Lee R, Malberg JE, Chen J, Steffen C, Zhang YJ, Nestler EJ, Duman RS

Abstract

The cAMP cascade, including the cAMP response element-binding protein (CREB), is known to play an important role in neuronal survival and plasticity. Here the influence of this cascade on neurogenesis in adult hippocampus was determined. Activation of the cAMP cascade by administration of rolipram, an inhibitor of cAMP breakdown, increased the proliferation of newborn cells in adult mouse hippocampus. In addition, rolipram induction of cell proliferation resulted in mature granule cells that express neuronal-specific markers. Increased cell proliferation is accompanied by activation of CREB phosphorylation in dentate gyrus granule cells, suggesting a role for this transcription factor. This possibility is supported by studies demonstrating that cell proliferation is decreased in conditional transgenic mice that express a dominant negative mutant of CREB in hippocampus. The results suggest that the cAMP-CREB cascade could contribute to the actions of neurotransmitters and neurotrophic factors on adult neurogenesis.

MeSH Terms
3',5'-Cyclic-AMP Phosphodiesterases/antagonists & inhibitors Amino Acid Substitution Animals Antigens, Differentiation/biosynthesis Bromodeoxyuridine Cell Count Cell Division/drug effects,physiology Cell Survival/drug effects Cyclic AMP/metabolism,pharmacology Cyclic AMP Response Element-Binding Protein/genetics,metabolism,pharmacology Cyclic Nucleotide Phosphodiesterases, Type 4 Genes, Dominant Hippocampus/cytology,drug effects,metabolism Mice Mice, Inbred C57BL Mice, Transgenic Neurons/cytology,drug effects,metabolism Phenotype Phosphodiesterase Inhibitors/pharmacology Phosphorylation/drug effects Rolipram/pharmacology Signal Transduction/drug effects
Chemicals
Antigens, Differentiation Cyclic AMP Response Element-Binding Protein Phosphodiesterase Inhibitors Cyclic AMP 3',5'-Cyclic-AMP Phosphodiesterases Cyclic Nucleotide Phosphodiesterases, Type 4 Bromodeoxyuridine Rolipram
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Nakagawa Shin
Division of Molecular Psychiatry, Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, Yale University School of Medicine, New Haven, Connecticut 06508, USA.
Kim Ji-Eun
Lee Rena
Malberg Jessica E
Chen Jingshan
Steffen Cathy
Zhang Ya-Jun
Nestler Eric J
Duman Ronald S
References (38)
38 references, click to expand
  1. NeuN, a neuronal specific nuclear protein in vertebrates.
    Development. 1992 Sep;116(1):201-11 PMID: 1483388
  2. The molecular biology of cyclic nucleotide phosphodiesterases.
    Prog Nucleic Acid Res Mol Biol. 1999;63:1-38 PMID: 10506827
  3. Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus.
    J Neurosci. 2000 Dec 15;20(24):9104-10 PMID: 11124987
  4. Unbiased stereological estimation of the total number of neurons in thesubdivisions of the rat hippocampus using the optical fractionator.
    Anat Rec. 1991 Dec;231(4):482-97 PMID: 1793176
  5. Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus.
    Nat Neurosci. 1999 Mar;2(3):266-70 PMID: 10195220
  6. CREB couples neurotrophin signals to survival messages.
    Neuron. 2000 Jan;25(1):11-4 PMID: 10707967
  7. Rolipram, a type IV-specific phosphodiesterase inhibitor, facilitates the establishment of long-lasting long-term potentiation and improves memory.
    Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):15020-5 PMID: 9844008
  8. Differentiation of newly born neurons and glia in the dentate gyrus of the adult rat.
    Neuroscience. 1993 Sep;56(2):337-44 PMID: 8247264
  9. Peripheral infusion of IGF-I selectively induces neurogenesis in the adult rat hippocampus.
    J Neurosci. 2000 Apr 15;20(8):2896-903 PMID: 10751442
  10. Adult-generated hippocampal and neocortical neurons in macaques have a transient existence.
    Proc Natl Acad Sci U S A. 2001 Sep 11;98(19):10910-7 PMID: 11526209
  11. cAMP response element-mediated gene transcription is upregulated by chronic antidepressant treatment.
    J Neurosci. 2000 Jun 1;20(11):4030-6 PMID: 10818138
  12. The adult rat hippocampus contains primordial neural stem cells.
    Mol Cell Neurosci. 1997;8(6):389-404 PMID: 9143557
  13. Hippocampal volume in geriatric depression.
    Biol Psychiatry. 2000 Aug 15;48(4):301-9 PMID: 10960161
  14. CREB and memory.
    Annu Rev Neurosci. 1998;21:127-48 PMID: 9530494
  15. Immunohistochemical co-localization of S-100b and the glial fibrillary acidic protein in rat brain.
    Neuroscience. 1986 Mar;17(3):857-65 PMID: 2422599
  16. Hippocampal atrophy in recurrent major depression.
    Proc Natl Acad Sci U S A. 1996 Apr 30;93(9):3908-13 PMID: 8632988
  17. Neurogenesis in the dentate gyrus of the adult tree shrew is regulated by psychosocial stress and NMDA receptor activation.
    J Neurosci. 1997 Apr 1;17(7):2492-8 PMID: 9065509
  18. Multipotent stem/progenitor cells with similar properties arise from two neurogenic regions of adult human brain.
    Exp Neurol. 1999 Apr;156(2):333-44 PMID: 10328940
  19. Neural consequences of environmental enrichment.
    Nat Rev Neurosci. 2000 Dec;1(3):191-8 PMID: 11257907
  20. Bromodeoxyuridine immunohistochemical determination of the lengths of the cell cycle and the DNA-synthetic phase for an anatomically defined population.
    J Neurocytol. 1989 Jun;18(3):311-8 PMID: 2746304
  21. Transgenic animals with inducible, targeted gene expression in brain.
    Mol Pharmacol. 1998 Sep;54(3):495-503 PMID: 9730908
  22. Chronic antidepressant administration increases the expression of cAMP response element binding protein (CREB) in rat hippocampus.
    J Neurosci. 1996 Apr 1;16(7):2365-72 PMID: 8601816
  23. Neurogenesis in the dentate gyrus of the adult rat: age-related decrease of neuronal progenitor proliferation.
    J Neurosci. 1996 Mar 15;16(6):2027-33 PMID: 8604047
  24. Learning enhances adult neurogenesis in the hippocampal formation.
    Nat Neurosci. 1999 Mar;2(3):260-5 PMID: 10195219
  25. Regulation of neurogenesis by growth factors and neurotransmitters.
    J Neurobiol. 1998 Aug;36(2):287-306 PMID: 9712310
  26. Cyclic AMP stimulates somatostatin gene transcription by phosphorylation of CREB at serine 133.
    Cell. 1989 Nov 17;59(4):675-80 PMID: 2573431
  27. CREB: a stimulus-induced transcription factor activated by a diverse array of extracellular signals.
    Annu Rev Biochem. 1999;68:821-61 PMID: 10872467
  28. Restoring production of hippocampal neurons in old age.
    Nat Neurosci. 1999 Oct;2(10):894-7 PMID: 10491610
  29. More hippocampal neurons in adult mice living in an enriched environment.
    Nature. 1997 Apr 3;386(6624):493-5 PMID: 9087407
  30. Retinoic acid and neurotrophins collaborate to regulate neurogenesis in adult-derived neural stem cell cultures.
    J Neurobiol. 1999 Jan;38(1):65-81 PMID: 10027563
  31. Neurogenesis in the adult human hippocampus.
    Nat Med. 1998 Nov;4(11):1313-7 PMID: 9809557
  32. Mammalian neural stem cells.
    Science. 2000 Feb 25;287(5457):1433-8 PMID: 10688783
  33. A modified tetracycline-regulated system provides autoregulatory, inducible gene expression in cultured cells and transgenic mice.
    Proc Natl Acad Sci U S A. 1995 Jul 3;92(14):6522-6 PMID: 7604026
  34. Neuronal plasticity and survival in mood disorders.
    Biol Psychiatry. 2000 Oct 15;48(8):732-9 PMID: 11063970
  35. Fibroblast growth factor-2/brain-derived neurotrophic factor-associated maturation of new neurons generated from adult human subependymal cells.
    Ann Neurol. 1998 May;43(5):576-85 PMID: 9585351
  36. Control of memory formation through regulated expression of a CaMKII transgene.
    Science. 1996 Dec 6;274(5293):1678-83 PMID: 8939850
  37. A molecular and cellular theory of depression.
    Arch Gen Psychiatry. 1997 Jul;54(7):597-606 PMID: 9236543
  38. Temporal control of gene expression in transgenic mice by a tetracycline-responsive promoter.
    Proc Natl Acad Sci U S A. 1994 Sep 27;91(20):9302-6 PMID: 7937760
Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
DOI
20026301
Published
2002-05-01
Pages
3673-82
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6758358
Subset
IM
Grants
NIMH NIH HHS · P01 MH025642 · United States
NIMH NIH HHS · 2 PO1 MH25642 · United States
NIMH NIH HHS · MH45481 · United States
NIMH NIH HHS · R37 MH045481 · United States
NIMH NIH HHS · R01 MH045481 · United States
External Links
PubMed source DOI: 20026301 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2