Skip to main content
Log in

A critical time window for the survival of neural progenitor cells by HDAC inhibitors in the hippocampus

  • Published:
Molecules and Cells

Abstract

Histone deacetylase inhibitors (HDACIs) that modulate gene expression by inhibiting HDAC enzymes may contribute to the survival of immature hippocampal neurons. However, it remains unknown how and when HDACIs regulate the survival of newly generated immature hippocampal neurons. In the present study, if the treatment of valproic acid (VPA) and sodium butyrate (SBt) in the specific time window during the development of newly generated n eurons r esulted in the i ncreased survival of bromodeoxyuridine (BrdU)(+) neurons in the dentate gyrus (DG) of hippocampus in mice was investigated. It was found that the number of BrdU(+) cells, the expressions of anti-apoptotic Bcl-2 family members and pCREB [D1] were increased by HDACIs when HDACIs were treated no later than 2–3 weeks after BrdU labeling. This suggests that epigenetic modification within a specific time window is critical for the survival of newborn hippocampal neurons by inhibiting the apoptotic pathway.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Ambrogini, P., Cuppini, R., Cuppini, C., Ciaroni, S., Cecchini, T., Ferri, P., Sartini, S., and Del Grande, P. (2000). Spatial learning affects immature granule cell survival in adult rat dentate gyrus. Neurosci. Lett. 286, 21–24.

    Article  PubMed  CAS  Google Scholar 

  • Chen, G., Zeng, W.Z., Yuan, P.X., Huang, L.D., Jiang, Y.M., Zhao, Z.H., and Manji, H.K. (1999). The mood-stabilizing agents lithium and valproate robustly increase the levels of the neuroprotective protein bcl-2 in the CNS. J. Neurochem. 72, 879–882.

    Article  PubMed  CAS  Google Scholar 

  • Chwang, W.B., Arthur, J.S., Schumacher, A., and Sweatt, J.D. (2007). The nuclear kinase mitogen- and stress-activated protein kinase 1 regulates hippocampal chromatin remodeling in memory formation. J. Neurosci. 27, 12732–12742.

    Article  PubMed  CAS  Google Scholar 

  • Dietz, G.P., Dietz, B., and Bahr, M. (2007). Bcl-xL protects cerebellar granule neurons against the late phase, but not against the early phase of glutamate-induced cell death. Brain Res. 1164, 136–141.

    Article  PubMed  CAS  Google Scholar 

  • Dupret, D., Fabre, A., Dobrossy, M.D., Panatier, A., Rodriguez, J.J., Lamarque, S., Lemaire, V., Oliet, S.H., Piazza, P.V., and Abrous, D.N. (2007). Spatial learning depends on both the addition and removal of new hippocampal neurons. PLoS Biol. 5, e214.

    Article  PubMed  Google Scholar 

  • Faraco, G., Pancani, T., Formentini, L., Mascagni, P., Fossati, G., Leoni, F., Moroni, F., and Chiarugi, A. (2006). Pharmacological inhibition of histone deacetylases by suberoylanilide hydroxamic acid specifically alters gene expression and reduces ischemic injury in the mouse brain. Mol. Pharmacol. 70, 1876–1884.

    Article  PubMed  CAS  Google Scholar 

  • Hansen, M.R., Roehm, P.C., Xu, N., and Green, S.H. (2007). Overexpression of Bcl-2 or Bcl-xL prevents spiral ganglion neuron death and inhibits neurite growth. Dev. Neurobiol. 67, 316–325.

    Article  PubMed  CAS  Google Scholar 

  • Jessberger, S., Nakashima, K., Clemenson, G.D., Jr., Mejia, E., Mathews, E., Ure, K., Ogawa, S., Sinton, C.M., Gage, F.H., and Hsieh, J. (2007). Epigenetic modulation of seizure-induced neuro- genesis and cognitive decline. J. Neurosci. 27, 5967–5975.

    Article  PubMed  CAS  Google Scholar 

  • Kanai, H., Sawa, A., Chen, R.W., Leeds, P., and Chuang, D.M. (2004). Valproic acid inhibits histone deacetylase activity and suppresses excitotoxicity-induced GAPDH nuclear accumulation and apoptotic death in neurons. Pharmacogenomics J. 4, 336–344.

    Article  PubMed  CAS  Google Scholar 

  • Kempermann, G., Kuhn, H.G., and Gage, F.H. (1998). Experience-induced neurogenesis in the senescent dentate gyrus. J. Neurosci. 18, 3206–3212.

    PubMed  CAS  Google Scholar 

  • Kempermann, G., Gast, D., Kronenberg, G., Yamaguchi, M., and Gage, F.H. (2003). Early determination and long-term persistence of adult-generated new neurons in the hippocampus of mice. Development 130, 391–399.

    Article  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 

  • Langley, B., D’Annibale, M.A., Suh, K., Ayoub, I., Tolhurst, A., Bastan, B., Yang, L., Ko, B., Fisher, M., Cho, S., et al. (2008). Pulse inhibition of histone deacetylases induces complete resistance to oxidative death in cortical neurons without toxicity and reveals a role for cytoplasmic p21(waf1/cip1) in cell cycleindependent neuroprotection. J. Neurosci. 28, 163–176.

    Article  PubMed  CAS  Google Scholar 

  • Le, Y.Z., Zheng, L., Le, Y., Rucker, E.B., 3rd, and Anderson, R.E. (2008). Role of BCL-XL in photoreceptor survival. Adv. Exp. Med. Biol. 613, 69–74.

    Article  PubMed  Google Scholar 

  • Levenson, J.M., O’Riordan, K.J., Brown, K.D., Trinh, M.A., Molfese, D.L., and Sweatt, J.D. (2004). Regulation of histone acetylation during memory formation in the hippocampus. J. Biol. Chem. 279, 40545–40559.

    Article  PubMed  CAS  Google Scholar 

  • Meller, R., Minami, M., Cameron, J.A., Impey, S., Chen, D., Lan, J. Q., Henshall, D.C., and Simon, R.P. (2005) CREB-mediated Bcl-2 protein expression after ischemic preconditioning. J. Cereb. Blood Flow Metab. 25, 234–246.

    Article  PubMed  CAS  Google Scholar 

  • Minamiyama, M., Katsuno, M., Adachi, H., Waza, M., Sang, C., Kobayashi, Y., Tanaka, F., Doyu, M., Inukai, A., and Sobue, G. (2004). Sodium butyrate ameliorates phenotypic expression in a transgenic mouse model of spinal and bulbar muscular atrophy. Hum. Mol. Genet. 13, 1183–1192.

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Ryu, H., Smith, K., Camelo, S.I., Carreras, I., Lee, J., Iglesias, A.H., Dangond, F., Cormier, K.A., Cudkowicz, M.E., Brown, R.H., Jr., et al. (2005) Sodium phenylbutyrate prolongs survival and regulates expression of anti-apoptotic genes in transgenic amyotrophic lateral sclerosis mice. J. Neurochem. 93, 1087–1098.

    Article  PubMed  CAS  Google Scholar 

  • Sasaki, T., Kitagawa, K., Yagita, Y., Sugiura, S., Omura-Matsuoka, E., Tanaka, S., Matsushita, K., Okano, H., Tsujimoto, Y., and Hori, M. (2006). Bcl2 enhances survival of newborn neurons in the normal and ischemic hippocampus. J. Neurosci. Res. 84, 1187–1196.

    Article  PubMed  CAS  Google Scholar 

  • Sisti, H.M., Glass, A.L., and Shors, T.J. (2007). Neurogenesis and the spacing effect: learning over time enhances memory and the survival of new neurons. Learn. Mem. 14, 368–375.

    Article  PubMed  Google Scholar 

  • Swaab, D.F. (1991). Brain aging and Alzheimer’s disease, “wear and tear” versus “use it or lose it”. Neurobiol. Aging 12, 317–324.

    Article  PubMed  CAS  Google Scholar 

  • Tashiro, A., Makino, H., and Gage, F.H. (2007). Experience-specific functional modification of the dentate gyrus through adult neurogenesis: a critical period during an immature stage. J. Neurosci. 27, 3252–3259.

    Article  PubMed  CAS  Google Scholar 

  • Thiagalingam, S., Cheng, K.H., Lee, H.J., Mineva, N., Thiagalingam, A., and Ponte, J.F. (2003). Histone deacetylases: unique players in shaping the epigenetic histone code. Ann. N Y Acad. Sci. 983, 84–100.

    Article  PubMed  CAS  Google Scholar 

  • Vecsey, C.G., Hawk, J.D., Lattal, K.M., Stein, J.M., Fabian, S.A., Attner, M.A., Cabrera, S.M., McDonough, C.B., Brindle, P.K., Abel, T., et al. (2007). Histone deacetylase inhibitors enhance memory and synaptic plasticity via CREB:CBP-dependent transcriptional activation. J. Neurosci. 27, 6128–6140.

    Article  PubMed  CAS  Google Scholar 

  • Zhang, R., Xue, Y.Y., Lu, S.D., Wang, Y., Zhang, L.M., Huang, Y.L., Signore, A.P., Chen, J., and Sun, F.Y. (2006). Bcl-2 enhances neurogenesis and inhibits apoptosis of newborn neurons in adult rat brain following a transient middle cerebral artery occlusion. Neurobiol. Dis. 24, 345–356.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Chang Ho Lee or Hyeon Son.

About this article

Cite this article

Kim, BW., Yang, S., Lee, C.H. et al. A critical time window for the survival of neural progenitor cells by HDAC inhibitors in the hippocampus. Mol Cells 31, 159–164 (2011). https://doi.org/10.1007/s10059-011-0019-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10059-011-0019-5

Keywords

Navigation