Skip to main content

Advertisement

SpringerLink
Log in

Time-Course of Changes in Phosphorylated CREB in Neuroblasts and BDNF in the Mouse Dentate Gyrus at Early Postnatal Stages

  • Short Communication
  • Published:
Cellular and Molecular Neurobiology Aims and scope Submit manuscript

Abstract

Cyclic AMP (cAMP) response element-binding protein (CREB) is involved in memory, learning, and synaptic transmission. In this study, we observed changes of phosphorylated CREB (pCREB) immunoreactivity and its protein levels as well as brain-derived neurotrophic factor (BDNF) levels in the hippocampal dentate gyrus at postnatal (P) 1, 7, 14, and 21 in mice. In addition, we also investigated pCREB expression in doublecortin (DCX, a marker for neuronal progenitors) immunoreactive neuroblasts at P21. pCREB immunoreaction at P1 was detected in most of cells in the dentate gyrus, thereafter pCREB immunoreactivity was decreased in all the layers of the dentate gyrus with time, however, strong pCREB immunoreactivity was shown in cells confined to the subgranular zone of the dentate gyrus at P21. In this group, many pCREB immunoreactive cells were co-localized with DCX immunoreactive neuroblasts. In addition, pCREB protein levels were decreased with age, showing that their levels were very low at P21, while BDNF protein levels were increased with age. These results suggest that pCREB may play important roles in functional maturity of granule cells in mice.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

References

  • Altman J (1975) Postnatal development of the cerebellar cortex in the rat. IV. Spatial organization of bipolar cells, parallel fibers and glial palisades. J Comp Neurol 163:427–447

    Article  PubMed  CAS  Google Scholar 

  • Andersen P (2007) The hippocampus book. Oxford University Press, New York

    Google Scholar 

  • Bain MJ, Dwyer SM, Rusak B (2004) Restraint stress affects hippocampal cell proliferation differently in rats and mice. Neurosci Lett 368:7–10

    Article  PubMed  CAS  Google Scholar 

  • Bayer SA, Altman J (1974) Hippocampal development in the rat: cytogenesis and morphogenesis examined with autoradiography and low-level X-irradiation. J Comp Neurol 158:55–79

    Article  PubMed  CAS  Google Scholar 

  • Bender RA, Lauterborn JC, Gall CM, Cariaga W, Baram TZ (2001) Enhanced CREB phosphorylation in immature dentate gyrus granule cells precedes neurotrophin expression and indicates a specific role of CREB in granule cell differentiation. Eur J Neurosci 13:679–686

    Article  PubMed  CAS  Google Scholar 

  • Finkbeiner S, Tavazoie SF, Maloratsky A, Jacobs KM, Harris KM, Greenberg ME (1997) CREB: a major mediator of neuronal neurotrophin responses. Neuron 19:1031–1047

    Article  PubMed  CAS  Google Scholar 

  • Friedman WJ, Olson L, Persson H (1991) Cells that express brain-derived neurotrophic factor mRNA in the developing postnatal rat brain. Eur J Neurosci 3:688–697

    Article  PubMed  Google Scholar 

  • Giachino C, De Marchis S, Giampietro C, Parlato R, Perroteau I, Schutz G, Fasolo A, Peretto P (2005) cAMP response element-binding protein regulates differentiation and survival of newborn neurons in the olfactory bulb. J Neurosci 25:10105–10118

    Article  PubMed  CAS  Google Scholar 

  • Hattiangady B, Rao MS, Shetty GA, Shetty AK (2005) Brain-derived neurotrophic factor, phosphorylated cyclic AMP response element binding protein and neuropeptide Y decline as early as middle age in the dentate gyrus and CA1 and CA3 subfields of the hippocampus. Exp Neurol 195:353–371

    Article  PubMed  CAS  Google Scholar 

  • Hwang IK, Yi SS, Shin JH, Yoo KY, Choi JH, Lee CH, Seong JK, Yoon YS, Park JH, Won MH (2010) Cyclosporine A reduces dendritic outgrowth of neuroblasts in the subgranular zone of the dentate gyrus in C57BL/6 mice. Neurochem Res 35:465–472

    Article  PubMed  CAS  Google Scholar 

  • Jagasia R, Steib K, Englberger E, Herold S, Faus-Kessler T, Saxe M, Gage FH, Song H, Lie DC (2009) GABA-cAMP response element-binding protein signaling regulates maturation and survival of newly generated neurons in the adult hippocampus. J Neurosci 29:7966–7977

    Article  PubMed  CAS  Google Scholar 

  • Katoh-Semba R, Asano T, Ueda H, Morishita R, Takeuchi IK, Inaguma Y, Kato K (2002) Riluzole enhances expression of brain-derived neurotrophic factor with consequent proliferation of granule precursor cells in the rat hippocampus. FASEB J 16:1328–1330

    PubMed  CAS  Google Scholar 

  • Kitagawa K (2007) CREB and cAMP response element-mediated gene expression in the ischemic brain. FEBS J 274:3210–3217

    Article  PubMed  CAS  Google Scholar 

  • Lee J, Duan W, Mattson MP (2002) Evidence that brain-derived neurotrophic factor is required for basal neurogenesis and mediates, in part, the enhancement of neurogenesis by dietary restriction in the hippocampus of adult mice. J Neurochem 82:1367–1375

    Article  PubMed  CAS  Google Scholar 

  • Li YF, Huang Y, Amsdell SL, Xiao L, O’Donnell JM, Zhang HT (2009) Antidepressant- and anxiolytic-like effects of the phosphodiesterase-4 inhibitor rolipram on behavior depend on cyclic AMP response element binding protein-mediated neurogenesis in the hippocampus. Neuropsychopharmacology 34:2404–2419

    Article  PubMed  CAS  Google Scholar 

  • McDonald HY, Wojtowicz JM (2005) Dynamics of neurogenesis in the dentate gyrus of adult rats. Neurosci Lett 385:70–75

    Article  PubMed  CAS  Google Scholar 

  • Nacher J, Crespo C, McEwen BS (2001) Doublecortin expression in the adult rat telencephalon. Eur J Neurosci 14:629–644

    Article  PubMed  CAS  Google Scholar 

  • Nakagawa S, Kim JE, Lee R, Chen J, Fujioka T, Malberg J, Tsuji S, Duman RS (2002) Localization of phosphorylated cAMP response element-binding protein in immature neurons of adult hippocampus. J Neurosci 22:9868–9876

    PubMed  CAS  Google Scholar 

  • Pencea V, Bingaman KD, Wiegand SJ, Luskin MB (2001) Infusion of brain-derived neurotrophic factor into the lateral ventricle of the adult rat leads to new neurons in the parenchyma of the striatum, septum, thalamus, and hypothalamus. J Neurosci 21:6706–6717

    PubMed  CAS  Google Scholar 

  • Pinnock SB, Herbert J (2008) Brain-derived neurotropic factor and neurogenesis in the adult rat dentate gyrus: interactions with corticosterone. Eur J Neurosci 27:2493–2500

    Article  PubMed  Google Scholar 

  • Sasaki T, Kitagawa K, Omura-Matsuoka E, Todo K, Terasaki Y, Sugiura S, Hatazawa J, Yagita Y, Hori M (2007) The phosphodiesterase inhibitor rolipram promotes survival of newborn hippocampal neurons after ischemia. Stroke 38:1597–1605

    Article  PubMed  CAS  Google Scholar 

  • Scharfman H, Goodman J, Macleod A, Phani S, Antonelli C, Croll S (2005) Increased neurogenesis and the ectopic granule cells after intrahippocampal BDNF infusion in adult rats. Exp Neurol 192:348–356

    Article  PubMed  CAS  Google Scholar 

  • Sibbe M, Forster E, Basak O, Taylor V, Frotscher M (2009) Reelin and Notch1 cooperate in the development of the dentate gyrus. J Neurosci 29:8578–8585

    Article  PubMed  CAS  Google Scholar 

  • Soriano E, Del Rio JA, Martinez A, Super H (1994) Organization of the embryonic and early postnatal murine hippocampus. I. Immunocytochemical characterization of neuronal populations in the subplate and marginal zone. J Comp Neurol 342:571–595

    Article  PubMed  CAS  Google Scholar 

  • Van der Borght K, Havekes R, Bos T, Eggen BJ, Van der Zee EA (2007) Exercise improves memory acquisition and retrieval in the Y-maze task: relationship with hippocampal neurogenesis. Behav Neurosci 121:324–334

    Article  PubMed  Google Scholar 

  • Waeber G, Habener JF (1991) Nuclear translocation and DNA recognition signals colocalized within the bZIP domain of cyclic adenosine 3′,5′-monophosphate response element-binding protein CREB. Mol Endocrinol 5:1431–1438

    Article  PubMed  CAS  Google Scholar 

  • Wang ZL, Cheng SM, Ma MM, Ma YP, Yang JP, Xu GL, Liu XF (2008) Intranasally delivered bFGF enhances neurogenesis in adult rats following cerebral ischemia. Neurosci Lett 446:30–35

    Article  PubMed  CAS  Google Scholar 

  • Yagita Y, Kitagawa K, Sasaki T, Terasaki Y, Todo K, Omura-Matsuoka E, Matsumoto M, Hori M (2006) Postischemic exercise decreases neurogenesis in the adult rat dentate gyrus. Neurosci Lett 409:24–29

    Article  PubMed  CAS  Google Scholar 

  • Zhu DY, Lau L, Liu SH, Wei JS, Lu YM (2004) Activation of cAMP-response-element-binding protein (CREB) after focal cerebral ischemia stimulates neurogenesis in the adult dentate gyrus. Proc Natl Acad Sci USA 101:9453–9457

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors would like to thank Mr. Seung Uk Lee and Mrs. Hyun Sook Kim for their technical help in this study. This research was supported by the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2010-0010580), and by the Regional Core Research Program funded by the Korea Ministry of Education, Science and Technology (Medical & Bio-material Research Center).

Author information

Authors and Affiliations

  1. Department of Anatomy and Cell Biology, College of Veterinary Medicine, and Research Institute for Veterinary Science, Seoul National University, Seoul, 151-742, South Korea

    In Koo Hwang, Dae Young Yoo, Ji Won Choi & Yeo Sung Yoon

  2. Department of Oral Anatomy, College of Dentistry, Gangneung-Wonju National University, Gangneung, 210-702, South Korea

    Ki-Yeon Yoo

  3. Laboratory of Veterinary Pharmacology, College of Veterinary Medicine, Seoul National University, Seoul, 151-742, South Korea

    Choong Hyun Lee

  4. Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, 200-701, South Korea

    Choong Hyun Lee & Moo-Ho Won

  5. Department of Anatomy, College of Veterinary Medicine, Kangwon National University, Chuncheon, 200-701, South Korea

    Jung Hoon Choi

Authors
  1. In Koo Hwang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ki-Yeon Yoo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dae Young Yoo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ji Won Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Choong Hyun Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jung Hoon Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yeo Sung Yoon
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Moo-Ho Won
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Moo-Ho Won.

Additional information

In Koo Hwang and Ki-Yeon Yoo contributed equally to this article.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hwang, I.K., Yoo, KY., Yoo, D.Y. et al. Time-Course of Changes in Phosphorylated CREB in Neuroblasts and BDNF in the Mouse Dentate Gyrus at Early Postnatal Stages. Cell Mol Neurobiol 31, 669–674 (2011). https://doi.org/10.1007/s10571-011-9686-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10571-011-9686-1

Keywords

Search

Navigation