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Role of modulatory mediator serotonin in induction of epigenetic processes during long-term memory formation in Helix

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Russian Journal of Genetics: Applied Research

Abstract

Epigenetic mechanisms of the long-term memory formation are a promising field in neurobiology. They include the posttranslational histone modifications, which leads to the chromatin remodeling and thereby influences the gene expression involved in learning. Mollusks are a popular model in neurobiology because they have a relatively simple CNS with giant neurons. We have previously found the strong induction of histone H3 acetylation and methylation during food aversion conditioning in Helix. We think that these processes are regulated by a modulatory mediator, serotonin, which plays an important role in avoidance behavior. To elucidate the influence of serotonin on the induction of epigenetic processes, we investigated the action of a nonselective antagonist of serotonin receptors, methiothepin, on acetylation and methylation of histone H3 during Helix training. We found that the treatment with methiothepin prevented the increase in methylation and acetylation of H3 in a snail’s CNS induced by training and impairs the long-term memory formation. The long-term memory formation in methiothepin-treated animals can be reversed by the treatment with histone deacetylase inhibitor, NaB. Our data confirm the important role of serotonin in the induction of the epigenetic processes during aversion conditioning in Helix.

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References

  • Abel, T. and Zukin, R.S., Epigenetic targets of HDAC inhibition in neurodegenerative and psychiatric disorders, Curr. Opin. Pharmacol., 2008, vol. 8, no. 1, pp. 57–64.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Abramova, M.S., Nistratova, V.L., Moskvitin, A.A., and Pivovarov, A.S., Methiothepin-sensitive serotonin receptors are involved in postsynaptic mechanism of sensitization of Helix lucorum escape reaction, Zh. Vyssh. Nervn. Deyat. im. I.P. Pavlova, 2005, vol. 55, no. 3, pp. 385–392.

    CAS  Google Scholar 

  • Akbarian, S. and Huang, H.S., Epigenetic regulation in human brain-focus on histone lysine methylation, Biol. Psychiatry, 2009, vol. 65, no. 3, pp. 198–203.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Alarcon, J.M., Malleret, G., Touzani, K., et al., Chromatin acetylation, memory, and LTP are impaired in CBP+/− mice: a model for the cognitive deficit in Rubistein-Taybi syndrome and its amelioration, Neuron, 2004, vol. 42, no. 6, pp. 947–959.

    Article  CAS  PubMed  Google Scholar 

  • Alberini, C.M., Transcription factors in long-term memory and synaptic plasticity, Physiol. Rev., 2009, vol. 89, no. 1, pp. 121–145.

    Article  CAS  PubMed  Google Scholar 

  • Balaban, P.M. and Zakharov, I.S., Obuchenie i razvitie: obshchaya osnova dvukh yavlenii (Learning and Development: A Common Basis of the Two Phenomena), Moscow: Nauka, 1992.

    Google Scholar 

  • Barbas, D., Desgroseillers, L., Castellucci, V.F., et al., Multiple serotonergic mechanisms contributing to sensitization in aplysia: evidence of diverse serotonin receptor subtypes, Learn. Mem., 2003, vol. 10, pp. 373–386.

    Article  PubMed Central  PubMed  Google Scholar 

  • Berger, S.L., The complex language of chromatin regulation during transcription, Nature, 2007, vol. 447, pp. 407–412.

    Article  CAS  PubMed  Google Scholar 

  • Bredy, T.W., Wu, H., Crego, C., et al., Histone modifications around individual BDNF gene promoters in prefrontal cortex are associated with extinction of conditioned fear, Learn. Mem., 2007, vol. 14, no. 4, pp. 268–276.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Danilova, A.B. and Grinkevich, L.N., Inability of juvenile snails for long-term memory formation depends on acetylation status of histone h3 and can be improved by nab treatment, PLoS ONE, 2012, vol. 7, e41828, pp. 1–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Danilova, A.B., Kharchenko, O.A., Shevchenko, K.G., and Grinkevich, L.N., Histone H3 acetylation is asymmetrically induced upon learning in identified neurons of the food aversion network in the mollusk Helix lucorum, Front. Behav. Neurosci., 2010, vol. 4, no. 180, pp. 1–7.

    Google Scholar 

  • Fischer, A., Sananbenesi, F., Wang, X., et al., Recovery of learning and memory is associated with chromatin remodeling, Nature, 2007, vol. 447, no. 7141, pp. 178–182.

    Article  CAS  PubMed  Google Scholar 

  • Gill, R.K., Kumar, A., Malhotra, P., et al., Regulation of intestinal serotonin transporter expression via epigenetic mechanisms: role of HDAC2, Am. J. Physiol. Cell Physiol., 2013, vol. 304, no. 4, pp. 334–341.

    Article  Google Scholar 

  • Grinkevich, L.N., Epigenetics and long-term memory formation, Ross. Fiziol. Zh. im. I.M. Sechenova, 2012a, vol. 98, no. 5, pp. 553–574.

    CAS  PubMed  Google Scholar 

  • Grinkevich, L.N., Investigation of histone H3 methylation during long term memory formation, Ross. Fiziol. Zh. im. I.M. Sechenova, 2012b, vol. 98, no. 9, pp. 1111–1118.

    CAS  PubMed  Google Scholar 

  • Grinkevich, L.N. and Vasil’ev, G.V., Possible mechanisms of the regulation of genes expression during learning, Neurosci. Behav. Physiol., 2000, vol. 30, no. 3, pp. 277–292.

    Article  CAS  PubMed  Google Scholar 

  • Grinkevich, L.N., Lisachev, P.D., Baranova, K.A., and Kharchenko, O.A., Comparative analysis of MAP/ERK-kinase activation in the CNS of animals with different capability for learning, Ross. Fiziol. Zh. im. I.M. Sechenova, 2006, vol. 92, no. 5, pp. 536–545.

    CAS  PubMed  Google Scholar 

  • Grinkevich, L.N., Lisachev, P.D., Kharchenko, O.A., and Vasil’ev, G.V., Expression of MAP/ERK kinase cascade corresponds to the ability to develop food aversion in terrestrial snail at different stages of ontogenesis, Brain Res., 2008, vol. 1187, pp. 12–19.

    Article  CAS  PubMed  Google Scholar 

  • Guan, Z., Giustetto, M., Lomvardas, S., et al., Integration of long-term-memory-related synaptic plasticity involves bidirectional regulation of gene expression and chromatin structure, Cell, 2002, vol. 111, no. 4, pp. 483–493.

    Article  CAS  PubMed  Google Scholar 

  • Guan, J.S., Haggarty, S.J., Giacometti, E., et al., HDAC2 negatively regulates memory formation and synaptic plasticity, Nature, 2009, vol. 459, no. 7243, pp. 55–60.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Gupta, S., Kim, S.Y., Artis, S., et al., Histone methylation regulates memory formation, J. Neurosci., 2010, vol. 30, no. 10, pp. 3589–3599.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Hart, A.K., Fioravante, D., Liu, R.Y., et al., Serotonin-mediated synapsin expression is necessary for long-term facilitation of the aplysia sensorimotor synapse, J. Neurosci., 2011, vol. 31, no. 50, pp. 18401–18411.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kandel, E.R., The molecular biology of memory storage: a dialogue between genes and synapses, Science, 2001, vol. 294, no. 5544, pp. 1030–1048.

    Article  CAS  PubMed  Google Scholar 

  • Kandel, E., The molecular biology of memory: cAMP, PKA, CRE, CREB-1, CREB-2, and CPEB, Mol. Brain, 2012, vol. 5, no. 14, pp. 1–12.

    Google Scholar 

  • Kharchenko, O.A., Grinkevich, V.V., Vorobiova, O.V., and Grinkevich, L.N., Learning-induced lateralized activation of the MAPK/ERK cascade in identified neurons of the food-aversion network in the mollusk Helix lucorum, Neurobiol. Learn. Mem., 2010, vol. 94, no. 2, pp. 158–166.

    Article  PubMed  Google Scholar 

  • Korzus, E., Rosenfeld, M.G., and Mayford, M., CBP histone acetyltransferase activity is a critical component of memory consolidation, Neuron, 2004, vol. 42, no. 6, pp. 961–972.

    Article  CAS  PubMed  Google Scholar 

  • Kuhn, M., Popovic, A., and Pezawas, L., Neuroplasticity and memory formation in major depressive disorder: an imaging genetics perspective on serotonin and BDNF, Restor. Neurol. Neurosci., 2013 [Epub ahead of print].

    Google Scholar 

  • Kurita, M., Holloway, T., Garcia-Bea, A., et al., HDAC2 regulates atypical antipsychotic responses through the modulation of mGlu2 promoter activity, Nat. Neurosci., 2012, vol. 15, no. 9, pp. 1245–1254.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kurita, M., Moreno, J.L., Holloway, T., et al., Repressive epigenetic changes at the mGlu2 promoter in frontal cortex of 5-HT2A knockout mice, Mol. Pharmacol., 2013, vol. 83, no. 6, pp. 1166–1175.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Levenson, J.M. and Sweatt, J.D., Epigenetic mechanisms: a common theme in vertebrate and invertebrate memory formation, Cell Mol. Life Sci., 2006, vol. 63, pp. 1009–1016.

    Article  CAS  PubMed  Google Scholar 

  • Levenson, J.M., O’riordan, K.J., Brown, K.D., et al., Regulation of histone acetylation during memory formation in the hippocampus, J. Biol. Chem., 2004, vol. 279, pp. 40545–40559.

    Article  CAS  PubMed  Google Scholar 

  • Ressler, K.J., Paschall, G., Zhou, X.L., and Davis, M., Regulation of synaptic plasticity genes during consolidation of fear conditioning, J. Neurosci., 2002, vol. 22, no. 18, pp. 7892–7902.

    CAS  PubMed  Google Scholar 

  • Shishkina, T.G. and Dygalo, N.N., Neurobiological mechanisms of depression and antidepressant therapy, Zh. Vyssh. Nervn. Deyat. im. I.P. Pavlova, 2010, vol. 60, no. 2, pp. 138–152.

    CAS  Google Scholar 

  • Solntseva, S.V. and Nikitin, V.P., [Neurochemical mechanisms of food aversion conditioning consolidation in snail Helix lucorum, Ross. Fiziol. Zh. im. I.M. Sechenova, 2008, vol. 94, no. 11, pp. 1259–1269.

    CAS  PubMed  Google Scholar 

  • Stadler, F., Kolb, G., Rubusch, L., et al., Histone methylation at gene promoters is associated with developmental regulation and region-specific expression of ionotropic and metabotropic glutamate receptors in human brain, J. Neurochem., 2005, vol. 94, no. 2, pp. 324–336.

    Article  CAS  PubMed  Google Scholar 

  • Strahl, B.D. and Allis, C.D., The language of covalent histone modifications, Nature, 2000, vol. 403, no. 6765, pp. 41–45.

    Article  CAS  PubMed  Google Scholar 

  • Takase, K., Oda, S., Kuroda, M., and Funato, H., Monoaminergic and neuropeptidergic neurons have distinct expression profiles of histone deacetylases, PLoS One, 2013, vol. 8, no. 3, e58473, pp. 1–19.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Wood, M.A., Hawk, J.D., and Abel, T., Combinatorial chromatin modifications and memory storage: a code for memory, Learn. Mem., 2006, vol. 13, pp. 241–244.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Yamawaki, Y., Fuchikami, M., Morinobu, S., et al., Anti-depressant-like effect of sodium butyrate (HDAC inhibitor) and its molecular mechanism of action in the rat hippocampus, World J. Biol. Psychiatry, 2012, vol. 13, no. 6, pp. 458–467.

    Article  PubMed  Google Scholar 

  • Zhao, J., Goldberg, J., Bremner, J.D., and Vaccadrino, V., Association between promoter methylation of serotonin transporter gene and depressive symptoms: a monozygotic twin study, Psychosom. Med., 2013, vol. 75, no. 6, pp. 523–529.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Pavlov Institute of Physiology, Russian Academy of Sciences, St. Petersburg, Russia

    L. N. Grinkevich & O. V. Vorobiova

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  1. L. N. Grinkevich
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  2. O. V. Vorobiova
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Correspondence to L. N. Grinkevich.

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Original Russian Text © L.N. Grinkevich, O.V. Vorobiova, 2014, published in Vavilovskii Zhurnal Genetiki i Selektsii, 2014, Vol. 18, No. 2, pp. 298–307.

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Grinkevich, L.N., Vorobiova, O.V. Role of modulatory mediator serotonin in induction of epigenetic processes during long-term memory formation in Helix . Russ J Genet Appl Res 4, 526–532 (2014). https://doi.org/10.1134/S2079059714060094

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  • DOI: https://doi.org/10.1134/S2079059714060094

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