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Effects of Specific Inhibitor of Phosphodiesterase 7 at the Late Stage of Long-Term Potentiation in Murine Hippocampal Slices

  • N. A. BeregovoiEmail author
  • M. V. Starostina
  • T. V. Lipina
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Second messengers cAMP and cGMP play an important role in synaptic plasticity and memory consolidation. The inhibitors of phosphodiesterases, enzymes hydrolyzing these cyclic nucleotides, are actively studied as potential drugs for the treatment of various cognitive disorders and depression. We studied the effects of a new inhibitor of phosphodiesterase 7 AGF2.20 on the formation of long-term potentiation in hippocampal slices. Administration of AGF2.20 (10 nM) in 90 min after weak tetanization prevented a decrease in the amplitude of excitatory post-synaptic potentials and stabilized long-term potentiation. These data attest to the involvement of phosphodiesterase 7 in the development of synaptic plasticity in the hippocampus. The inhibitor AGF2.20 is considered for the further analysis as a promising substance for the treatment of cognitive impairments.

Key Words

phosphodiesterase synaptic plasticity inhibitors 

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References

  1. 1.
    Ahmad F, Murata T, Shimizu K, Degerman E, Maurice D, Manganiello V. Cyclic Nucleotide Phosphodiesterases: important signaling modulators and therapeutic targets. Oral Dis. 2015;21(1):e25-e50.CrossRefGoogle Scholar
  2. 2.
    Barad M, Bourtchouladze R, Winder DG, Golan H, Kandel E. Rolipram, a type IV-specific phosphodiesterase inhibitor, facilitates the establishment of long-lasting long-term potentiation and improves memory. Proc. Natl Acad. Sci. USA. 1998;95(25):15 020-15 025.CrossRefGoogle Scholar
  3. 3.
    Bliss TV, Collingridge GL, Morris RG. Synaptic plasticity in health and disease: introduction and overview. Philos. Trans. R Soc. Lond. B Biol. Sci. 2014;369. ID 20130129. doi:  https://doi.org/10.1098/rstb.2013.0129.
  4. 4.
    Blokland A, Menniti FS, Prickaerts J. PDE Inhibition and cognition enhancement. Expert Opin. Ther. Pat. 2012;22(4):349-354.CrossRefGoogle Scholar
  5. 5.
    Bollen E, Akkerman S, Puzzo D, Gulisano W, Palmeri A, D’Hooge R, Balschun D, Steinbusch H. W, Blokland A, Prickaerts J. Object memory enhancement by combining sub-efficacious doses of specific phosphodiesterase inhibitors. Neuropharmacology. 2015;95:361-366.CrossRefGoogle Scholar
  6. 6.
    Bollen E, Puzzo D, Rutten K, Privitera L, De Vry J, Vanmierlo T, Kenis G, Palmeri A, D’Hooge R, Balschun D, Steinbusch H. M, Blokland A, Prickaerts J. Improved long-term memory via enhancing cGMP-PKG signaling requires cAMP-PKA signaling. Neuropsychopharmacology. 2014;39(11):2497-2505.CrossRefGoogle Scholar
  7. 7.
    Francis SH, Blount MA, Corbin JD. Mammalian cyclic nucleotide phosphodiesterases: molecular mechanisms and physiological functions. Physiol. Rev. 2011;91(2):651-690.CrossRefGoogle Scholar
  8. 8.
    García AM, Brea J, Morales-García JA, Perez DI, González A, Alonso-Gil S, Gracia-Rubio I, Ros-Simó C, Conde S, Cadavid MI, Loza MI, Perez-Castillo A, Valverde O, Martinez A, Gil C. Modulation of cAMP-specific PDE without emetogenic activity: new sulfide-like PDE7 inhibitors. J. Med. Chem. 2014;57(20):8590-8607.CrossRefGoogle Scholar
  9. 9.
    Gewald R, Rueger C, Grunwald C, Egerland U, Hoefgen N. Synthesis and structure-activity relationship studies of dihydronaphthyridinediones as a novel structural class of potent and selective PDE7 inhibitors. Bioorg. Med. Chem. Lett. 2011;21(22):6652-6656.CrossRefGoogle Scholar
  10. 10.
    Johansson EM, Reyes-Irisarri E, Mengod G. Comparison of cAMP-specific phosphodiesterase mRNAs distribution in mouse and rat brain. Neurosci. Lett. 2012;525(1):1-6.CrossRefGoogle Scholar
  11. 11.
    Lipina TV, Beregovoy NA, Tkachenko AA, Petrova ES, Starostina MV, Zhou Q, Li S. Uncoupling DISC1*D2R proteinprotein interactions facilitates latent inhibition in Disc1-L100P animal model of schizophrenia and enhances synaptic plasticity via D2 receptors. Front. Synaptic Neurosci. 2018;10. ID 31. doi:  https://doi.org/10.3389/fnsyn.2018.00031.
  12. 12.
    Lipina TV, Jekielek M, Beregovoy NA, Starostina MV, Palomo V, Perez DI, Martinez A, Roder JC. Inhibition of glycogen synthase kinase 3 prevents synaptic long-term depression and facilitates cognition in C57Bl/6J mice. Opera Medica et Physiologica. 2016;2(3):87-102. doi:  https://doi.org/10.20388/OMP2016.002.0026.Google Scholar
  13. 13.
    Nicoll RA. A Brief history of long-term potentiation. Neuron. 2017;93(2):281-290.CrossRefGoogle Scholar
  14. 14.
    Sanderson TM, Sher E. The role of phosphodiesterases in hippocampal synaptic plasticity. Neuropharmacology. 2013;74:86-95.CrossRefGoogle Scholar
  15. 15.
    Xu Y, Zhang HT, O’Donnell JM. Phosphodiesterases in the central nervous system: implications in mood and cognitive disorders. Handb. Exp. Pharmacol. 2011;(204):447-485.CrossRefGoogle Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • N. A. Beregovoi
    • 1
    Email author
  • M. V. Starostina
    • 1
  • T. V. Lipina
    • 2
  1. 1.Research Institute of Molecular Biology and BiophysicsFederal Research Center of Fundamental and Translational MedicineNovosibirskRussia
  2. 2.Research Institute of Physiology and Fundamental MedicineNovosibirskRussia

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