Toxicological Research

Korean Society of Toxicology & Korea Environmental Mutagen Society (한국독성학회)
권호 표지
DOI QR코드

DOI QR Code

Promotion of cAMP Responsive Element-Binding Protein Activity Ameliorates Radiation-Induced Suppression of Hippocampal Neurogenesis in Adult Mice

  • Kim, Joong-Sun (Department of Veterinary Anatomy and Veterinary Toxicology, College of Veterinary Medicine and Animal Medical Institute, Chonnam National University) ;
  • Yang, Mi-Young (Department of Veterinary Anatomy and Veterinary Toxicology, College of Veterinary Medicine and Animal Medical Institute, Chonnam National University) ;
  • Cho, Jae-Ho (Department of Veterinary Anatomy and Veterinary Toxicology, College of Veterinary Medicine and Animal Medical Institute, Chonnam National University) ;
  • Kim, Sung-Ho (Department of Veterinary Anatomy and Veterinary Toxicology, College of Veterinary Medicine and Animal Medical Institute, Chonnam National University) ;
  • Kim, Jong-Choon (Department of Veterinary Anatomy and Veterinary Toxicology, College of Veterinary Medicine and Animal Medical Institute, Chonnam National University) ;
  • Shin, Tae-Kyun (Department of Veterinary Anatomy, College of Veterinary Medicine and Applied Radiological Science Research Institute, Cheju National University) ;
  • Moon, Chang-Jong (Department of Veterinary Anatomy and Veterinary Toxicology, College of Veterinary Medicine and Animal Medical Institute, Chonnam National University)
  • Received : 2010.07.30
  • Accepted : 2010.08.15
  • Published : 2010.09.01
Download PDF
⟨ Previous Next ⟩

Abstract

This study was performed to examine whether elevated activity of cAMP responsive element-binding protein (CREB) attenuates the detrimental effects of acute gamma ($\gamma$)-irradiation on hippocampal neurogenesis and related functions. C57BL/6 male mice were treated with rolipram (1.25 mg/kg, i.p., twice a day for 5 consecutive days) to activate the cAMP/CREB pathway against cranial irradiation (2 Gy), and were euthanized at 24 h post-irradiation. Exposure to $\gamma$-rays decreased both CREB phosphorylation and immunohistochemical markers for neurogenesis, including Ki-67 and doublecortin (DCX), in the hippocampal dentate gyrus (DG). However, the rolipram treatment protected from $\gamma$-irradiation-induced decreases of CREB phosphorylation, and Ki-67 and DCX immunoreactivity in the hippocampal DG. In an object recognition memory test, mice trained 24 h after acute $\gamma$-irradiation (2 Gy) showed significant memory impairment, which was attenuated by rolipram treatment. The results suggest that activation of CREB signaling ameliorates the detrimental effects of acute $\gamma$-irradiation on hippocampal neurogenesis and related functions in adult mice.

Keywords

References

  1. Barad, M. (2003). Later developments: molecular keys to agerelated memory impairment. Alzheimer Dis. Assoc. Disord., 17, 168-176. https://doi.org/10.1097/00002093-200307000-00009
  2. Barad, M., Bourtchouladze, R., Winder, D.G., Golan, H. and Kandel, E. (1998). 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., 95, 15020-15025. https://doi.org/10.1073/pnas.95.25.15020
  3. Bender, R.A., Lauterborn, J.C., Gall, C.M., Cariaga, W. and Baram, T.Z. (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. https://doi.org/10.1046/j.1460-9568.2001.01432.x
  4. Beshay, E., Croze, F. and Prud'homme, G.J. (2001). The phosphodiesterase inhibitors pentoxifylline and rolipram suppress macrophage activation and nitric oxide production in vitro and in vivo. Clin. Immunol., 98, 272-279. https://doi.org/10.1006/clim.2000.4964
  5. Brindle, P.K. and Montminy, M.R. (1992). The CREB family of transcription activators. Curr. Opin. Genet. Dev., 2, 199-204. https://doi.org/10.1016/S0959-437X(05)80274-6
  6. Bourtchouladze, R., Lidge, R., Catapano, R., Stanley, J., Gossweiler, S., Romashko, D., Scott, R. and Tully, T. (2003). A mouse model of Rubinstein-Taybi syndrome: defective longterm memory is ameliorated by inhibitors of phosphodiesterase 4. Proc. Natl. Acad. Sci. U.S.A., 100, 10518-10522. https://doi.org/10.1073/pnas.1834280100
  7. Bourtchuladze, R., Frenguelli, B., Blendy, J., Cioffi, D., Schutz, G. and Silva, A.J. (1994). Deficient long-term memory in mice with a targeted mutation of the cAMP-responsive element-binding protein. Cell, 79, 59-68. https://doi.org/10.1016/0092-8674(94)90400-6
  8. Coleman, C.N., Stone, H.B., Moulder, J.E. and Pellmar, T.C. (2004). Medicine. Modulation of radiation injury. Science, 304, 693-694. https://doi.org/10.1126/science.1095956
  9. Crossen, J.R., Garwood, D., Glatstein, E. and Neuwelt, E.A. (1994). Neurobehavioral sequelae of cranial irradiation in adults: a review of radiation-induced encephalopathy. J. Clin. Oncol., 12, 627-642. https://doi.org/10.1200/JCO.1994.12.3.627
  10. Davis, G.W., Schuster, C.M. and Goodman, C.S. (1996). Genetic dissection of structural and functional components of synaptic plasticity. III. CREB is necessary for presynaptic functional plasticity. Neuron, 17, 669-679. https://doi.org/10.1016/S0896-6273(00)80199-3
  11. Dinter, H., Tse, J., Halks-Miller, M., Asarnow, D., Onuffer, J., Faulds, D., Mitrovic, B., Kirsch, G., Laurent, H., Esperling, P., Seidelmann, D., Ottow, E., Schneider, H., Tuohy, V.K., Wachtel, H. and Perez, H.D. (2000). The type IV phosphodiesterase specific inhibitor mesopram inhibits experimental autoimmune encephalomyelitis in rodents. J. Neuroimmunol., 108, 136-146. https://doi.org/10.1016/S0165-5728(00)00265-4
  12. Finkbeiner, S. (2000). CREB couples neurotrophin signals to survival messages. Neuron, 25, 11-14. https://doi.org/10.1016/S0896-6273(00)80866-1
  13. Gong, B., Vitolo, O.V., Trinchese, F., Liu, S., Shelanski, M. and Arancio, O. (2004). Persistent improvement in synaptic and cognitive functions in an Alzheimer mouse model after rolipram treatment. J. Clin. Invest., 114, 1624-1634. https://doi.org/10.1172/JCI22831
  14. Gonzalez, G.A. and Montminy, M.R. (1989). Cyclic AMP stimulates somatostatin gene transcription by phosphorylation of CREB at serine 133. Cell, 59, 675-680. https://doi.org/10.1016/0092-8674(89)90013-5
  15. Hattiangady, B., Rao, M.S., Shetty, G.A. and Shetty, A.K. (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. https://doi.org/10.1016/j.expneurol.2005.05.014
  16. Kim, J.S., Lee, H.J., Kim, J.C., Kang, S.S., Bae, C.S., Shin, T., Jin, J.K., Kim, S.H., Wang, H. and Moon, C. (2008). Transient impairment of hippocampus-dependent learning and memory in relatively low-dose of acute radiation syndrome is associated with inhibition of hippocampal neurogenesis. J. Radiat. Res., 49, 517-526. https://doi.org/10.1269/jrr.08020
  17. Madsen, T.M., Kristjansen, P.E., Bolwig, T.G. and Wortwein, G.(2003). Arrested neuronal proliferation and impaired hippocampal function following fractionated brain irradiation in the adult rat. Neuroscience, 119, 635-642. https://doi.org/10.1016/S0306-4522(03)00199-4
  18. Meyers, C.A. and Brown, P.D. (2006). Role and relevance of neurocognitive assessment in clinical trials of patients with CNS tumors. J. Clin. Oncol., 24, 1305-1309. https://doi.org/10.1200/JCO.2005.04.6086
  19. Monti, B., Berteotti, C. and Contestabile, A. (2006). Subchronic rolipram delivery activates hippocampal CREB and arc, enhances retention and slows down extinction of conditioned fear. Neuropsychopharmacology, 31, 278-286. https://doi.org/10.1038/sj.npp.1300813
  20. Myhrer, T. (1989). Exploratory behavior, reaction to novelty, and proactive memory in rats with temporo-entorhinal connections disrupted. Physiol. Behav., 45, 431-436. https://doi.org/10.1016/0031-9384(89)90151-0
  21. Nagakura, A., Niimura, M. and Takeo, S. (2002). Effects of a phosphodiesterase IV inhibitor rolipram on microsphere embolism- induced defects in memory function and cerebral cyclic AMP signal transduction system in rats. Br. J. Pharmacol., 135, 1783-1793. https://doi.org/10.1038/sj.bjp.0704629
  22. Nakagawa, S., Kim, J.E., Lee, R., Malberg, J.E., Chen, J., Steffen, C., Zhang, Y.J., Nestler, E. J. and Duman, R.S. (2002). Regulation of neurogenesis in adult mouse hippocampus by cAMP and the cAMP response element-binding protein. J. Neurosci., 22, 3673-3682.
  23. Navakkode, S., Sajikumar, S. and Frey, J.U. (2004). The type IVspecific phosphodiesterase inhibitor rolipram and its effect on hippocampal long-term potentiation and synaptic tagging. J. Neurosci., 24, 7740-7744. https://doi.org/10.1523/JNEUROSCI.1796-04.2004
  24. Nibuya, M., Nestler, E.J. and Duman, R.S. (1996). Chronic antidepressant administration increases the expression of cAMP response element binding protein (CREB) in rat hippocampus. J. Neurosci., 16, 2365-2372.
  25. Posner, J.B. (1992). Management of brain metastases. Rev. Neurol., 148, 477-487.
  26. Silva, A.J., Stevens, C.F., Tonegawa, S. and Wang, Y. (1992). Deficient hippocampal long-term potentiation in alpha-calciumcalmodulin kinase II mutant mice. Science, 257, 201-206, https://doi.org/10.1126/science.1378648
  27. Stone, H.B., Coleman, C.N., Anscher, M.S. and McBride, W.H. (2003). Effects of radiation on normal tissue: consequences and mechanisms. Lancet. Oncol., 4, 529-536. https://doi.org/10.1016/S1470-2045(03)01191-4
  28. Vitolo, O.V., Sant'Angelo, A., Costanzo, V., Battaglia, F., Arancio, O. and Shelanski, M. (2002). Amyloid beta-peptide inhibition of the PKA/CREB pathway and long-term potentiation: reversibility by drugs that enhance cAMP signaling. Proc. Natl. Acad. Sci. U.S.A., 99, 13217-13221. https://doi.org/10.1073/pnas.172504199
  29. Yang, M., Kim, J.S., Song, M.S., Kim, S.H., Kang, S.S., Bae, C.S., Kim, J.C., Wang, H., Shin, T. and Moon, C. (2010). Cyclophosphamide impairs hippocampus-dependent learning and memory in adult mice: Possible involvement of hippocampal neurogenesis in chemotherapy-induced memory deficits. Neurobiol. Learn. Mem., 93, 487-494. https://doi.org/10.1016/j.nlm.2010.01.006
  30. Zhang, H.T., Zhao, Y., Huang, Y., Dorairaj, N.R., Chandler, L.J. and O'Donnell, J.M. (2004). Inhibition of the phosphodiesterase 4 (PDE4) enzyme reverses memory deficits produced by infusion of the MEK inhibitor U0126 into the CA1 subregion of the rat hippocampus. Neuropsychopharmacol., 29, 1432-1439. https://doi.org/10.1038/sj.npp.1300440

Cited by

  1. Effects of total saponins of Panax notoginseng on immature neuroblasts in the adult olfactory bulb following global cerebral ischemia/reperfusion vol.10, pp.9, 2015, https://doi.org/10.4103/1673-5374.165514
  2. Neonatal Irradiation Leads to Persistent Proteome Alterations Involved in Synaptic Plasticity in the Mouse Hippocampus and Cortex vol.14, pp.11, 2015, https://doi.org/10.1021/acs.jproteome.5b00564
  3. Protective Effect of Administered Rolipram against Radiation-Induced Testicular Injury in Mice vol.33, pp.1, 2015, https://doi.org/10.5534/wjmh.2015.33.1.20