Longevity, enhanced memory, and altered density of dendritic spines in hippocampal CA3 and dentate gyrus after hemizygous deletion of Pde2a in mice

Baillie GS, Tejeda GS, Kelly MP. Therapeutic targeting of 3’,5’-cyclic nucleotide phosphodiesterases: inhibition and beyond. Nat Rev. Drug Discov. 2019;18:770–96.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Heckman PRA, Blokland A, Bollen EPP, Prickaerts J. Phosphodiesterase inhibition and modulation of corticostriatal and hippocampal circuits: clinical overview and translational considerations. Neurosci Biobehav Rev. 2018;87:233–54.

Article  CAS  PubMed  Google Scholar 

Maurice DH, Ke H, Ahmad F, Wang Y, Chung J, Manganiello VC. Advances in targeting cyclic nucleotide phosphodiesterases. Nat Rev Drug Discov. 2014;13:290–314.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Martinez SE, Wu AY, Glavas NA, Tang XB, Turley S, Hol WG, et al. The two GAF domains in phosphodiesterase 2A have distinct roles in dimerization and in cGMP binding. Proc Natl Acad Sci. USA. 2002;99:13260–5.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Martins TJ, Mumby MC, Beavo JA. Purification and characterization of a cyclic GMP-stimulated cyclic nucleotide phosphodiesterase from bovine tissues. J Biol Chem. 1982;257:1973–9.

Article  CAS  PubMed  Google Scholar 

Lakics V, Karran EH, Boess FG. Quantitative comparison of phosphodiesterase mRNA distribution in human brain and peripheral tissues. Neuropharmacology. 2010;59:367–74.

Article  CAS  PubMed  Google Scholar 

Russwurm C, Zoidl G, Koesling D, Russwurm M. Dual acylation of PDE2A splice variant 3: targeting to synaptic membranes. J Biol Chem. 2009;284:25782–90.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Stephenson DT, Coskran TM, Kelly MP, Kleiman RJ, Morton D, O'Neill SM, et al. The distribution of phosphodiesterase 2A in the rat brain. Neuroscience. 2012;226:145–55.

Article  CAS  PubMed  Google Scholar 

Stephenson DT, Coskran TM, Wilhelms MB, Adamowicz WO, O'Donnell MM, Muravnick KB, et al. Immunohistochemical localization of phosphodiesterase 2A in multiple mammalian species. J Histochem Cytochem. 2009;57:933–49.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Boess FG, Hendrix M, van der Staay FJ, Erb C, Schreiber R, van Staveren W, et al. Inhibition of phosphodiesterase 2 increases neuronal cGMP, synaptic plasticity and memory performance. Neuropharmacology. 2004;47:1081–92.

Article  CAS  PubMed  Google Scholar 

Bollen E, Puzzo D, Rutten K, Privitera L, De Vry J, Vanmierlo T, et al. Improved long-term memory via enhancing cGMP-PKG signaling requires cAMP-PKA signaling. Neuropsychopharmacology. 2014;39:2497–505.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lueptow LM, Zhan CG, O’Donnell JM. Cyclic GMP-mediated memory enhancement in the object recognition test by inhibitors of phosphodiesterase-2 in mice. Psychopharmacology (Berl). 2016;233:447–56.

Article  CAS  PubMed  Google Scholar 

Rutten K, Prickaerts J, Hendrix M, van der Staay FJ, Sik A, Blokland A. Time-dependent involvement of cAMP and cGMP in consolidation of object memory: studies using selective phosphodiesterase type 2, 4 and 5 inhibitors. Eur J Pharmacol. 2007;558:107–12.

Article  CAS  PubMed  Google Scholar 

Rutten K, Van Donkelaar EL, Ferrington L, Blokland A, Bollen E, Steinbusch HW, et al. Phosphodiesterase inhibitors enhance object memory independent of cerebral blood flow and glucose utilization in rats. Neuropsychopharmacology. 2009;34:1914–25.

Article  CAS  PubMed  Google Scholar 

McQuown S, Xia S, Baumgärtel K, Barido R, Anderson G, Dyck B, et al. Phosphodiesterase 1b (PDE1B) regulates spatial and contextual memory in hippocampus. Front Mol Neurosci. 2019;12:21.

Article  PubMed  PubMed Central  Google Scholar 

Gomez L, Breitenbucher JG. PDE2 inhibition: potential for the treatment of cognitive disorders. Bioorg Med Chem Lett. 2013;23:6522–7.

Article  CAS  PubMed  Google Scholar 

Gomez L, Massari ME, Vickers T, Freestone G, Vernier W, Ly K, et al. Design and synthesis of novel and selective phosphodiesterase 2 (PDE2a) inhibitors for the treatment of memory disorders. J Med Chem. 2017;60:2037–51.

Article  CAS  PubMed  Google Scholar 

Helal CJ, Arnold EP, Boyden TL, Chang C, Chappie TA, Fennell KF, et al. Application of structure-based design and parallel chemistry to identify a potent, selective, and brain penetrant phosphodiesterase 2A inhibitor. J Med Chem. 2017;60:5673–98.

Article  CAS  PubMed  Google Scholar 

Mikami S, Sasaki S, Asano Y, Ujikawa O, Fukumoto S, Nakashima K, et al. Discovery of an orally bioavailable, brain-penetrating, in vivo active phosphodiesterase 2A inhibitor lead series for the Treatment of cognitive disorders. J Med Chem. 2017;60:7658–76.

Article  CAS  PubMed  Google Scholar 

Redrobe JP, Jørgensen M, Christoffersen CT, Montezinho LP, Bastlund JF, Carnerup M, et al. In vitro and in vivo characterisation of Lu AF64280, a novel, brain penetrant phosphodiesterase (PDE) 2A inhibitor: potential relevance to cognitive deficits in schizophrenia. Psychopharmacology (Berl). 2014;231:3151–67.

Article  CAS  PubMed  Google Scholar 

Stachel SJ, Berger R, Nomland AB, Ginnetti AT, Paone DV, Wang D, et al. Structure-guided design and procognitive assessment of a potent and selective phosphodiesterase 2A inhibitor. ACS Med Chem Lett. 2018;9:815–20.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Stachel SJ, Egbertson MS, Wai J, Machacek M, Toolan DM, Swestock J, et al. Indole acids as a novel PDE2 inhibitor chemotype that demonstrate pro-cognitive activity in multiple species. Bioorg Med Chem Lett. 2018;28:1122–6.

Article  CAS  PubMed  Google Scholar 

Paes D, Xie K, Wheeler DG, Zook D, Prickaerts J, Peters M. Inhibition of PDE2 and PDE4 synergistically improves memory consolidation processes. Neuropharmacology. 2021;184:108414.

Article  PubMed  Google Scholar 

Fernandez-Fernandez D, Rosenbrock H, Kroker KS. Inhibition of PDE2A, but not PDE9A, modulates presynaptic short-term plasticity measured by paired-pulse facilitation in the CA1 region of the hippocampus. Synapse. 2015;69:484–96.

Article  CAS  PubMed  Google Scholar 

Nakashima M, Imada H, Shiraishi E, Ito Y, Suzuki N, Miyamoto M, et al. Phosphodiesterase 2A inhibitor TAK-915 ameliorates cognitive impairments and social withdrawal in N-Methyl-d-aspartate receptor antagonist-induced rat models of schizophrenia. J Pharmacol Exp Ther. 2018;365:179–88.

Article  CAS  PubMed  Google Scholar 

Nakashima M, Suzuki N, Shiraishi E, Iwashita H. TAK-915, a phosphodiesterase 2A inhibitor, ameliorates the cognitive impairment associated with aging in rodent models. Behav Brain Res. 2019;376:112192.

Article  PubMed  Google Scholar 

Gu G, Scott T, Yan Y, Warren N, Zhang A, Tabatabaei A, et al. Target engagement of a phosphodiesterase 2A inhibitor affecting long-term memory in the Rat. J Pharmacol Exp Ther. 2019;370:399–407.

Article  CAS  PubMed  Google Scholar 

Van Staveren WC, Steinbusch HW, Markerink-Van Ittersum M, Repaske DR, Goy MF, Kotera J, et al. mRNA expression patterns of the cGMP-hydrolyzing phosphodiesterases types 2, 5, and 9 during development of the rat brain. J Comp Neurol. 2003;467:566–80.

Article  PubMed  Google Scholar 

Masood A, Huang Y, Hajjhussein H, Xiao L, Li H, Wang W, et al. Anxiolytic effects of phosphodiesterase-2 inhibitors associated with increased cGMP signaling. J Pharmacol Exp Ther. 2009;331:690–9.

Article  CAS  PubMed  PubMed Central 

Comments (0)

No login
gif