Abstract
Cyclic nucleotide phosphodiesterase (PDE) enzymes catalyze the hydrolysis and inactivation of cyclic nucleotides (cAMP/cGMP) in the brain. Several classes of PDE enzymes with distinct tissue distributions, cyclic nucleotide selectivity, and regulatory factors are highly expressed in brain regions subserving cognitive and motor processes known to be disrupted in neurodegenerative diseases such as Parkinson’s disease (PD). Furthermore, small-molecule inhibitors of several different PDE family members alter cyclic nucleotide levels and favorably enhance motor performance and cognition in animal disease models. This chapter will explore the roles and therapeutic potential of non-selective and selective PDE inhibitors on neural processing in fronto-striatal circuits in normal animals and models of DOPA-induced dyskinesias (LIDs) associated with PD. The impact of selective PDE inhibitors and augmentation of cAMP and cGMP signaling on the membrane excitability of striatal medium-sized spiny projection neurons (MSNs) will be discussed. The effects of cyclic nucleotide signaling and PDE inhibitors on synaptic plasticity of striatonigral and striatopallidal MSNs will be also be reviewed. New data on the efficacy of PDE10A inhibitors for reversing behavioral and electrophysiological correlates of L-DOPA-induced dyskinesias in a rat model of PD will also be presented. Together, these data will highlight the potential of novel PDE inhibitors for treatment of movement disorders such as PD which are associated with abnormal corticostriatal transmission.
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References
Alderton WK, Cooper CE, Knowles RG. Nitric oxide synthases: structure, function and inhibition. Biochem J. 2001;357(Pt 3):593–615.
Andersson M, Hilbertson A, Cenci MA. Striatal fosB expression is causally linked with l-DOPA-induced abnormal involuntary movements and the associated upregulation of striatal prodynorphin mRNA in a rat model of Parkinson's disease. Neurobiol Dis. 1999;6(6):461–474. doi:S0969-9961(99)90259-0 [pii]. doi:10.1006/nbdi.1999.0259.
Ariano MA. Distribution of components of the guanosine 3′,5′-phosphate system in rat caudate-putamen. Neuroscience. 1983;10(3):707–23. doi:0306-4522(83)90212-9 [pii]
Ashman DF, Lipton R, Melicow MM, Price TD. Isolation of adenosine 3′, 5′-monophosphate and guanosine 3′, 5′-monophosphate from rat urine. Biochem Biophys Res Commun. 1963;11:330–4.
Augustin SM, Beeler JA, McGehee DS, Zhuang X. Cyclic AMP and afferent activity govern bidirectional synaptic plasticity in striatopallidal neurons. J Neurosci. 2014;34(19):6692–9. doi:10.1523/JNEUROSCI.3906-13.2014.
Bateup HS, Santini E, Shen W, Birnbaum S, Valjent E, Surmeier DJ, Fisone G, Nestler EJ, Greengard P. Distinct subclasses of medium spiny neurons differentially regulate striatal motor behaviors. Proc Natl Acad Sci U S A. 2010;107(33):14845–50. doi:1009874107 [pii]10.1073/pnas.1009874107
Beeler JA, Frank MJ, McDaid J, Alexander E, Turkson S, Bernardez Sarria MS, McGehee DS, Zhuang X. A role for dopamine-mediated learning in the pathophysiology and treatment of Parkinson's disease. Cell Rep. 2012;2(6):1747–61. doi:10.1016/j.celrep.2012.11.014.
Bender AT, Beavo JA. Cyclic nucleotide phosphodiesterases: molecular regulation to clinical use. Pharmacol Rev. 2006;58(3):488–520. doi:10.1124/pr.58.3.5.
Bernard V, Normand E, Bloch B. Phenotypical characterization of the rat striatal neurons expressing muscarinic receptor genes. J Neurosci. 1992;12(9):3591–600.
Berthet J, Rall TW, Sutherland EW. The relationship of epinephrine and glucagon to liver phosphorylase. IV. Effect of epinephrine and glucagon on the reactivation of phosphorylase in liver homogenates. J Biol Chem. 1957;224(1):463–75.
Berton O, Guigoni C, Li Q, Bioulac BH, Aubert I, Gross CE, Dileone RJ, Nestler EJ, Bezard E. Striatal overexpression of DeltaJunD resets L-DOPA-induced dyskinesia in a primate model of Parkinson disease. Biol Psychiatry. 2009;66(6):554–61. doi:S0006-3223(09)00447-8 [pii]10.1016/j.biopsych.2009.04.005
Boehning D, Snyder SH. Novel neural modulators. Annu Rev Neurosci. 2003;26:105–31. doi:10.1146/annurev.neuro.26.041002.131047.
Bredt DS. Nitric oxide signaling specificity--the heart of the problem. J Cell Sci. 2003;116(Pt 1):9–15.
Bredt DS, Hwang PM, Snyder SH. Localization of nitric oxide synthase indicating a neural role for nitric oxide. Nature. 1990;347(6295):768–70. doi:10.1038/347768a0.
Calabresi P, Maj R, Pisani A, Mercuri NB, Bernardi G. Long-term synaptic depression in the striatum: physiological and pharmacological characterization. J Neurosci. 1992a;12(11):4224–33.
Calabresi P, Maj R, Mercuri NB, Bernardi G. Coactivation of D1 and D2 dopamine receptors is required for long-term synaptic depression in the striatum. Neurosci Lett. 1992b;142(1):95–9.
Calabresi P, Maj R, Pisani A, Mercuri NB, Bernardi G. Long-term synaptic depression in the striatum: physiological and pharmacological characterization. J Neurosci. 1992c;12(11):4224–33.
Calabresi P, Pisani A, Centonze D, Bernardi G. Synaptic plasticity and physiological interactions between dopamine and glutamate in the striatum. Neurosci Biobehav Rev. 1997a;21(4):519–23. doi:S0149-7634(96)00029-2 [pii]
Calabresi P, Saiardi A, Pisani A, Baik JH, Centonze D, Mercuri NB, Bernardi G, Borrelli E. Abnormal synaptic plasticity in the striatum of mice lacking dopamine D2 receptors. J Neurosci. 1997b;17(12):4536–44.
Calabresi P, Gubellini P, Centonze D, Sancesario G, Morello M, Giorgi M, Pisani A, Bernardi G. A critical role of the nitric oxide/cGMP pathway in corticostriatal long-term depression. J Neurosci. 1999;19(7):2489–99.
Calabresi P, Gubellini P, Centonze D, Picconi B, Bernardi G, Chergui K, Svenningsson P, Fienberg AA, Greengard P. Dopamine and cAMP-regulated phosphoprotein 32 kDa controls both striatal long-term depression and long-term potentiation, opposing forms of synaptic plasticity. J Neurosci. 2000;20(22):8443–51. doi:20/22/8443 [pii]
Calabresi P, Picconi B, Tozzi A, Di Filippo M. Dopamine-mediated regulation of corticostriatal synaptic plasticity. Trends Neurosci. 2007;30(5):211–9. doi:S0166-2236(07)00048-3 [pii]10.1016/j.tins.2007.03.001
Carter AG, Sabatini BL. State-dependent calcium signaling in dendritic spines of striatal medium spiny neurons. Neuron. 2004;44(3):483–93. doi:10.1016/j.neuron.2004.10.013.
Cenci M, Tranberg A, Andersson M, Hilbertson A. Changes in the regional and compartmental distribution of FosB- and JunB-like immunoreactivity induced in the dopamine-denervated rat striatum by acute or chronic L-dopa treatment. Neuroscience. 1999;94(2):515–27. doi:S0306-4522(99)00294-8 [pii]
Centonze D, Gubellini P, Picconi B, Calabresi P, Giacomini P, Bernardi G. Unilateral dopamine denervation blocks corticostriatal LTP. J Neurophysiol. 1999;82(6):3575–9.
Centonze D, Grande C, Saulle E, Martin AB, Gubellini P, Pavon N, Pisani A, Bernardi G, Moratalla R, Calabresi P. Distinct roles of D1 and D5 dopamine receptors in motor activity and striatal synaptic plasticity. J Neurosci. 2003;23(24):8506–12.
Charpier S, Deniau JM. In vivo activity-dependent plasticity at cortico-striatal connections: evidence for physiological long-term potentiation. Proc Natl Acad Sci U S A. 1997;94(13):7036–40.
Charych EI, Jiang LX, Lo F, Sullivan K, Brandon NJ. Interplay of palmitoylation and phosphorylation in the trafficking and localization of phosphodiesterase 10A: implications for the treatment of schizophrenia. J Neurosci. 2010;30(27):9027–37. doi:10.1523/JNEUROSCI.1635-10.2010.
Cherry JA, Davis RL. Cyclic AMP phosphodiesterases are localized in regions of the mouse brain associated with reinforcement, movement, and affect. J Comp Neurol. 1999;407(2):287–301.
Choi S, Lovinger DM. Decreased probability of neurotransmitter release underlies striatal long-term depression and postnatal development of corticostriatal synapses. Proc Natl Acad Sci U S A. 1997;94(6):2665–70.
Colwell CS, Levine MS. Excitatory synaptic transmission in neostriatal neurons: regulation by cyclic AMP-dependent mechanisms. J Neurosci. 1995;15(3 Pt 1):1704–13.
Conti M, Beavo J. Biochemistry and physiology of cyclic nucleotide phosphodiesterases: essential components in cyclic nucleotide signaling. Annu Rev Biochem. 2007;76:481–511. doi:10.1146/annurev.biochem.76.060305.150444.
Coskran TM, Morton D, Menniti FS, Adamowicz WO, Kleiman RJ, Ryan AM, Strick CA, Schmidt CJ, Stephenson DT. Immunohistochemical localization of phosphodiesterase 10A in multiple mammalian species. J Histochem Cytochem. 2006;54(11):1205–13. doi:10.1369/jhc.6A6930.2006.
Darmopil S, Martín AB, De Diego IR, Ares S, Moratalla R. Genetic inactivation of dopamine D1 but not D2 receptors inhibits L-DOPA-induced dyskinesia and histone activation. Biol Psychiatry. 2009;66(6):603–13. doi:10.1016/j.biopsych.2009.04.025.
Ding JD, Burette A, Nedvetsky PI, Schmidt HH, Weinberg RJ. Distribution of soluble guanylyl cyclase in the rat brain. J Comp Neurol. 2004;472(4):437–48. doi:10.1002/cne.20054.
Feyder M, Bonito-Oliva A, Fisone G. L-DOPA-induced dyskinesia and abnormal signaling in striatal medium spiny neurons: focus on dopamine D1 receptor-mediated transmission. Front Behav Neurosci. 2011;5:71. doi:10.3389/fnbeh.2011.00071.
Fisher DA, Smith JF, Pillar JS, St Denis SH, Cheng JB. Isolation and characterization of PDE9A, a novel human cGMP-specific phosphodiesterase. J Biol Chem. 1998;273(25):15559–64.
Garthwaite J. Concepts of neural nitric oxide-mediated transmission. Eur J Neurosci. 2008;27(11):2783–802. doi:10.1111/j.1460-9568.2008.06285.x.
Gentzel RC, Toolan D, Roberts R, Koser AJ, Kandebo M, Hershey J, Renger JJ, Uslaner J, Smith SM. The PDE10A inhibitor MP-10 and haloperidol produce distinct gene expression profiles in the striatum and influence cataleptic behavior in rodents. Neuropharmacology. 2015;99:256–63. doi:10.1016/j.neuropharm.2015.05.024.
Gerdeman GL, Ronesi J, Lovinger DM. Postsynaptic endocannabinoid release is critical to long-term depression in the striatum. Nat Neurosci. 2002;5(5):446–51. doi:10.1038/nn832.
Gerfen CR, Young WS 3rd. Distribution of striatonigral and striatopallidal peptidergic neurons in both patch and matrix compartments: an in situ hybridization histochemistry and fluorescent retrograde tracing study. Brain Res. 1988;460(1):161–7.
Gerfen CR, Miyachi S, Paletzki R, Brown P. D1 dopamine receptor supersensitivity in the dopamine-depleted striatum results from a switch in the regulation of ERK1/2/MAP kinase. J Neurosci. 2002;22(12):5042–54.
Gilman AG. G proteins: transducers of receptor-generated signals. Annu Rev Biochem. 1987;56:615–49. doi:10.1146/annurev.bi.56.070187.003151.
Giorgi M, D'Angelo V, Esposito Z, Nuccetelli V, Sorge R, Martorana A, Stefani A, Bernardi G, Sancesario G. Lowered cAMP and cGMP signalling in the brain during levodopa-induced dyskinesias in hemiparkinsonian rats: new aspects in the pathogenetic mechanisms. Eur J Neurosci. 2008;28(5):941–50. doi:EJN6387 [pii]10.1111/j.1460-9568.2008.06387.x
de Gortari P, Mengod G. Dopamine D1, D2 and mu-opioid receptors are co-expressed with adenylyl cyclase 5 and phosphodiesterase 7B mRNAs in striatal rat cells. Brain Res. 2010;1310:37–45. doi:10.1016/j.brainres.2009.11.009.
Grauer SM, Pulito VL, Navarra RL, Kelly MP, Kelley C, Graf R, Langen B, Logue S, Brennan J, Jiang L, Charych E, Egerland U, Liu F, Marquis KL, Malamas M, Hage T, Comery TA, Brandon NJ. Phosphodiesterase 10A inhibitor activity in preclinical models of the positive, cognitive, and negative symptoms of schizophrenia. J Pharmacol Exp Ther. 2009;331(2):574–90. doi:10.1124/jpet.109.155994.
Greengard P, Allen PB, Nairn AC. Beyond the dopamine receptor: the DARPP-32/protein phosphatase-1 cascade. Neuron. 1999;23(3):435–47.
Gubellini P, Saulle E, Centonze D, Bonsi P, Pisani A, Bernardi G, Conquet F, Calabresi P. Selective involvement of mGlu1 receptors in corticostriatal LTD. Neuropharmacology. 2001;40(7):839–46.
Hemmings HC Jr, Greengard P. DARPP-32, a dopamine- and adenosine 3′:5′-monophosphate-regulated phosphoprotein: regional, tissue, and phylogenetic distribution. J Neurosci. 1986;6(5):1469–81.
Hemmings HC Jr, Greengard P, Tung HY, Cohen P. DARPP-32, a dopamine-regulated neuronal phosphoprotein, is a potent inhibitor of protein phosphatase-1. Nature. 1984;310(5977):503–5.
Hersch SM, Gutekunst CA, Rees HD, Heilman CJ, Levey AI. Distribution of m1-m4 muscarinic receptor proteins in the rat striatum: light and electron microscopic immunocytochemistry using subtype-specific antibodies. J Neurosci. 1994;14(5 Pt 2):3351–63.
Hofmann M, Spano PF, Trabucchi M, Kumakura K. Guanylate cyclase activity in various rat brain areas. J Neurochem. 1977;29(2):395–6.
Huang CC, Hsu KS. Progress in understanding the factors regulating reversibility of long-term potentiation. Rev Neurosci. 2001;12(1):51–68.
Huot P, Johnston TH, Koprich JB, Fox SH, Brotchie JM. The pharmacology of L-DOPA-induced dyskinesia in Parkinson's disease. Pharmacol Rev. 2013;65(1):171–222. doi:10.1124/pr.111.005678.
Kawaguchi Y, Wilson CJ, Augood SJ, Emson PC. Striatal interneurones: chemical, physiological and morphological characterization. Trends Neurosci. 1995;18(12):527–35. doi:0166223695983748 [pii]
Kerr JN, Plenz D. Dendritic calcium encodes striatal neuron output during up-states. J Neurosci. 2002;22(5):1499–512.
Kerr JN, Wickens JR. Dopamine D-1/D-5 receptor activation is required for long-term potentiation in the rat neostriatum in vitro. J Neurophysiol. 2001;85(1):117–24.
Kheirbek MA, Britt JP, Beeler JA, Ishikawa Y, McGehee DS, Zhuang X. Adenylyl cyclase type 5 contributes to corticostriatal plasticity and striatum-dependent learning. J Neurosci. 2009;29(39):12115–24. doi:10.1523/JNEUROSCI.3343-09.2009.
Kleiman RJ, Chapin DS, Christoffersen C, Freeman J, Fonseca KR, Geoghegan KF, Grimwood S, Guanowsky V, Hajos M, Harms JF, Helal CJ, Hoffmann WE, Kocan GP, Majchrzak MJ, McGinnis D, McLean S, Menniti FS, Nelson F, Roof R, Schmidt AW, Seymour PA, Stephenson DT, Tingley FD, Vanase-Frawley M, Verhoest PR, Schmidt CJ. Phosphodiesterase 9A regulates central cGMP and modulates responses to cholinergic and monoaminergic perturbation in vivo. J Pharmacol Exp Ther. 2012;341(2):396–409. doi:10.1124/jpet.111.191353.
Kotera J, Sasaki T, Kobayashi T, Fujishige K, Yamashita Y, Omori K. Subcellular localization of cyclic nucleotide phosphodiesterase type 10A variants, and alteration of the localization by cAMP-dependent protein kinase-dependent phosphorylation. J Biol Chem. 2004;279(6):4366–75. doi:10.1074/jbc.M308471200.
Kreitzer AC, Malenka RC. Dopamine modulation of state-dependent endocannabinoid release and long-term depression in the striatum. J Neurosci. 2005;25(45):10537–45. doi:10.1523/JNEUROSCI.2959-05.2005.
Kreitzer AC, Malenka RC. Striatal plasticity and basal ganglia circuit function. Neuron. 2008;60(4):543–54. doi:10.1016/j.neuron.2008.11.005.
Lane E, Dunnett S. Animal models of Parkinson's disease and L-dopa induced dyskinesia: how close are we to the clinic? Psychopharmacology. 2008;199(3):303–12. doi:10.1007/s00213-007-0931-8.
Lebel M, Chagniel L, Bureau G, Cyr M. Striatal inhibition of PKA prevents levodopa-induced behavioural and molecular changes in the hemiparkinsonian rat. Neurobiol Dis. 2010;38(1):59–67. doi:S0969-9961(09)00382-9 [pii]10.1016/j.nbd.2009.12.027
Leuti A, Laurenti D, Giampa C, Montagna E, Dato C, Anzilotti S, Melone MA, Bernardi G, Fusco FR. Phosphodiesterase 10A (PDE10A) localization in the R6/2 mouse model of Huntington's disease. Neurobiol Dis. 2013;52:104–16. doi:10.1016/j.nbd.2012.11.016.
Lin DT, Fretier P, Jiang C, Vincent SR. Nitric oxide signaling via cGMP-stimulated phosphodiesterase in striatal neurons. Synapse. 2010;64(6):460–6. doi:10.1002/syn.20750.
Lorenc-Koci E, Czarnecka A, Lenda T, Kaminska K, Konieczny J. Molsidomine, a nitric oxide donor, modulates rotational behavior and monoamine metabolism in 6-OHDA lesioned rats treated chronically with L-DOPA. Neurochem Int. 2013;63(8):790–804. doi:10.1016/j.neuint.2013.09.021.
Maries E, Kordower JH, Chu Y, Collier TJ, Sortwell CE, Olaru E, Shannon K, Steece-Collier K. Focal not widespread grafts induce novel dyskinetic behavior in parkinsonian rats. Neurobiol Dis. 2006;21(1):165–80. doi:10.1016/j.nbd.2005.07.002.
Martinez SE, Wu AY, Glavas NA, Tang XB, Turley S, Hol WG, Beavo JA. The two GAF domains in phosphodiesterase 2A have distinct roles in dimerization and in cGMP binding. Proc Natl Acad Sci U S A. 2002;99(20):13260–5. doi:10.1073/pnas.192374899.
Matsuoka I, Giuili G, Poyard M, Stengel D, Parma J, Guellaen G, Hanoune J. Localization of adenylyl and guanylyl cyclase in rat brain by in situ hybridization: comparison with calmodulin mRNA distribution. J Neurosci. 1992;12(9):3350–60.
Megens AA, Hendrickx HM, Hens KA, Fonteyn I, Langlois X, Lenaerts I, Somers MV, de Boer P, Vanhoof G. Pharmacology of JNJ-42314415, a centrally active phosphodiesterase 10A (PDE10A) inhibitor: a comparison of PDE10A inhibitors with D2 receptor blockers as potential antipsychotic drugs. J Pharmacol Exp Ther. 2014;349(1):138–54. doi:10.1124/jpet.113.211904.
Menniti FS, Faraci WS, Schmidt CJ. Phosphodiesterases in the CNS: targets for drug development. Nat Rev Drug Discov. 2006;5(8):660–70. doi:nrd2058 [pii]10.1038/nrd2058
Meredith GE, Sonsalla PK, Chesselet MF. Animal models of Parkinson's disease progression. Acta Neuropathol. 2008;115(4):385–98. doi:10.1007/s00401-008-0350-x.
Miro X, Perez-Torres S, Palacios JM, Puigdomenech P, Mengod G. Differential distribution of cAMP-specific phosphodiesterase 7A mRNA in rat brain and peripheral organs. Synapse. 2001;40(3):201–14. doi:10.1002/syn.1043.
Mons N, Decorte L, Jaffard R, Cooper DM. Ca2+−sensitive adenylyl cyclases, key integrators of cellular signalling. Life Sci. 1998;62(17–18):1647–52.
Murad F. Nitric oxide: the coming of the second messenger. Rambam Maimonides Med J. 2011;2(2):e0038. doi:10.5041/RMMJ.10038.
Niccolini F, Haider S, Reis Marques T, Muhlert N, Tziortzi AC, Searle GE, Natesan S, Piccini P, Kapur S, Rabiner EA, Gunn RN, Tabrizi SJ, Politis M. Altered PDE10A expression detectable early before symptomatic onset in Huntington's disease. Brain. 2015;138(Pt 10):3016–29. doi:10.1093/brain/awv214.
Nishi A, Watanabe Y, Higashi H, Tanaka M, Nairn AC, Greengard P. Glutamate regulation of DARPP-32 phosphorylation in neostriatal neurons involves activation of multiple signaling cascades. Proc Natl Acad Sci U S A. 2005;102(4):1199–204. doi:0409138102 [pii]10.1073/pnas.0409138102
Nishi A, Kuroiwa M, Miller DB, O'Callaghan JP, Bateup HS, Shuto T, Sotogaku N, Fukuda T, Heintz N, Greengard P, Snyder GL. Distinct roles of PDE4 and PDE10A in the regulation of cAMP/PKA signaling in the striatum. J Neurosci. 2008;28(42):10460–71. doi:10.1523/JNEUROSCI.2518-08.2008.
Ondracek JM, Dec A, Hoque KE, Lim SA, Rasouli G, Indorkar RP, Linardakis J, Klika B, Mukherji SJ, Burnazi M, Threlfell S, Sammut S, West AR. Feed-forward excitation of striatal neuron activity by frontal cortical activation of nitric oxide signaling in vivo. Eur J Neurosci. 2008;27(7):1739–54. doi:EJN6157 [pii]10.1111/j.1460-9568.2008.06157.x
Ouimet CC, Greengard P. Distribution of DARPP-32 in the basal ganglia: an electron microscopic study. J Neurocytol. 1990;19(1):39–52.
Ouimet CC, LaMantia AS, Goldman-Rakic P, Rakic P, Greengard P. Immunocytochemical localization of DARPP-32, a dopamine and cyclic-AMP-regulated phosphoprotein, in the primate brain. J Comp Neurol. 1992;323(2):209–18. doi:10.1002/cne.903230206.
Ouimet CC, Langley-Gullion KC, Greengard P. Quantitative immunocytochemistry of DARPP-32-expressing neurons in the rat caudatoputamen. Brain Res. 1998;808(1):8–12.
Padovan-Neto FE, Echeverry MB, Tumas V, Del-Bel EA. Nitric oxide synthase inhibition attenuates L-DOPA-induced dyskinesias in a rodent model of Parkinson's disease. Neuroscience. 2009;159(3):927–35. doi:S0306-4522(09)00091-8 [pii]10.1016/j.neuroscience.2009.01.034
Padovan-Neto FE, Cavalcanti-Kiwiatkoviski R, Carolino RO, Anselmo-Franci J, Del Bel E. Effects of prolonged neuronal nitric oxide synthase inhibition on the development and expression of L-DOPA-induced dyskinesia in 6-OHDA-lesioned rats. Neuropharmacology. 2015a;89:87–99. doi:10.1016/j.neuropharm.2014.08.019.
Padovan-Neto FE, Sammut S, Chakroborty S, Dec AM, Threlfell S, Campbell PW, Mudrakola V, Harms JF, Schmidt CJ, West AR. Facilitation of corticostriatal transmission following pharmacological inhibition of striatal phosphodiesterase 10A: role of nitric oxide-soluble guanylyl cyclase-cGMP signaling pathways. J Neurosci. 2015b;35(14):5781–91. doi:10.1523/JNEUROSCI.1238-14.2015.
Pavón N, Martín A, Mendialdua A, Moratalla R. ERK phosphorylation and FosB expression are associated with L-DOPA-induced dyskinesia in hemiparkinsonian mice. Biol Psychiatry. 2006;59(1):64–74. doi:S0006-3223(05)00707-9 [pii]10.1016/j.biopsych.2005.05.044
Perez-Torres S, Miro X, Palacios JM, Cortes R, Puigdomenech P, Mengod G. Phosphodiesterase type 4 isozymes expression in human brain examined by in situ hybridization histochemistry and[3H]rolipram binding autoradiography. Comparison with monkey and rat brain. J Chem Neuroanat. 2000;20(3–4):349–74.
Perreault ML, Hasbi A, Alijaniaram M, Fan T, Varghese G, Fletcher PJ, Seeman P, O'Dowd BF, George SR. The dopamine D1-D2 receptor heteromer localizes in dynorphin/enkephalin neurons: increased high affinity state following amphetamine and in schizophrenia. J Biol Chem. 2010;285(47):36625–34. doi:10.1074/jbc.M110.159954.
Picconi B, Centonze D, Håkansson K, Bernardi G, Greengard P, Fisone G, Cenci MA, Calabresi P. Loss of bidirectional striatal synaptic plasticity in L-DOPA-induced dyskinesia. Nat Neurosci. 2003;6(5):501–6. doi:nn1040 [pii]10.1038/nn1040
Picconi B, Paialle V, Ghiglieri V, Bagetta V, Barone I, Lindgren HS, Bernardi G, Cenci MA, Calabresi P. L-DOPA dosage is critically involved in dyskinesia via loss of synaptic depotentiation. Neurobiology of Disease. 2008;29:327–35. doi:10.1016/j.nbd.2007.10.001|ISSN 0969-9961
Picconi B, Bagetta V, Ghiglieri V, Paillè V, Di Filippo M, Pendolino V, Tozzi A, Giampà C, Fusco FR, Sgobio C, Calabresi P. Inhibition of phosphodiesterases rescues striatal long-term depression and reduces levodopa-induced dyskinesia. Brain. 2011;134(Pt 2):375–87. doi:awq342 [pii]10.1093/brain/awq342
Polito M, Klarenbeek J, Jalink K, Paupardin-Tritsch D, Vincent P, Castro LR. The NO/cGMP pathway inhibits transient cAMP signals through the activation of PDE2 in striatal neurons. Front Cell Neurosci. 2013;7:211. doi:10.3389/fncel.2013.00211.
Polito M, Guiot E, Gangarossa G, Longueville S, Doulazmi M, Valjent E, Herve D, Girault JA, Paupardin-Tritsch D, Castro LR, Vincent P. Selective effects of PDE10A inhibitors on striatopallidal neurons require phosphatase inhibition by DARPP-32(1,2,3). eNeuro. 2015;2(4):24. doi:10.1523/ENEURO.0060-15.2015.
Polli JW, Kincaid RL. Expression of a calmodulin-dependent phosphodiesterase isoform (PDE1B1) correlates with brain regions having extensive dopaminergic innervation. J Neurosci. 1994;14(3 Pt 1):1251–61.
Rafalovich IV, Melendez AE, Plotkin JL, Tanimura A, Zhai S, Surmeier DJ. Interneuronal nitric oxide signaling mediates post-synaptic long-term depression of striatal Glutamatergic synapses. Cell Rep. 2015;13(7):1336–42. doi:10.1016/j.celrep.2015.10.015.
Reed TM, Repaske DR, Snyder GL, Greengard P, Vorhees CV. Phosphodiesterase 1B knock-out mice exhibit exaggerated locomotor hyperactivity and DARPP-32 phosphorylation in response to dopamine agonists and display impaired spatial learning. J Neurosci. 2002;22(12):5188–97.
Reyes-Irisarri E, Perez-Torres S, Mengod G. Neuronal expression of cAMP-specific phosphodiesterase 7B mRNA in the rat brain. Neuroscience. 2005;132(4):1173–85. doi:10.1016/j.neuroscience.2005.01.050.
Reyes-Irisarri E, Markerink-Van Ittersum M, Mengod G, de Vente J. Expression of the cGMP-specific phosphodiesterases 2 and 9 in normal and Alzheimer's disease human brains. Eur J Neurosci. 2007;25(11):3332–8. doi:10.1111/j.1460-9568.2007.05589.x.
Ronesi J, Gerdeman GL, Lovinger DM. Disruption of endocannabinoid release and striatal long-term depression by postsynaptic blockade of endocannabinoid membrane transport. J Neurosci. 2004;24(7):1673–9. doi:10.1523/JNEUROSCI.5214-03.2004.
Russwurm C, Zoidl G, Koesling D, Russwurm M. Dual acylation of PDE2A splice variant 3: targeting to synaptic membranes. J Biol Chem. 2009;284(38):25782–90. doi:10.1074/jbc.M109.017194.
Russwurm C, Koesling D, Russwurm M. Phosphodiesterase 10A is tethered to a synaptic signaling complex in striatum. J Biol Chem. 2015;290(19):11936–47. doi:10.1074/jbc.M114.595769.
Sagi Y, Heiman M, Peterson JD, Musatov S, Scarduzio M, Logan SM, Kaplitt MG, Surmeier DJ, Heintz N, Greengard P. Nitric oxide regulates synaptic transmission between spiny projection neurons. Proc Natl Acad Sci U S A. 2014;111(49):17636–41. doi:10.1073/pnas.1420162111.
Sammut S, Park DJ, West AR. Frontal cortical afferents facilitate striatal nitric oxide transmission in vivo via a NMDA receptor and neuronal NOS-dependent mechanism. J Neurochem. 2007;103(3):1145–56. doi:JNC4811 [pii]10.1111/j.1471-4159.2007.04811.x
Sammut S, Threlfell S, West AR. Nitric oxide-soluble guanylyl cyclase signaling regulates corticostriatal transmission and short-term synaptic plasticity of striatal projection neurons recorded in vivo. Neuropharmacology. 2010;58(3):624–31. doi:S0028-3908(09)00359-1 [pii]10.1016/j.neuropharm.2009.11.011
Sancesario G, Morrone LA, D'Angelo V, Castelli V, Ferrazzoli D, Sica F, Martorana A, Sorge R, Cavaliere F, Bernardi G, Giorgi M. Levodopa-induced dyskinesias are associated with transient down-regulation of cAMP and cGMP in the caudate-putamen of hemiparkinsonian rats: reduced synthesis or increased catabolism? Neurochem Int. 2014;79:44–56. doi:10.1016/j.neuint.2014.10.004.
Santini E, Valjent E, Usiello A, Carta M, Borgkvist A, Girault JA, Herve D, Greengard P, Fisone G. Critical involvement of cAMP/DARPP-32 and extracellular signal-regulated protein kinase signaling in L-DOPA-induced dyskinesia. J Neurosci. 2007;27(26):6995–7005. doi:10.1523/JNEUROSCI.0852-07.2007.
Santini E, Alcacer C, Cacciatore S, Heiman M, Hervé D, Greengard P, Girault JA, Valjent E, Fisone G. L-DOPA activates ERK signaling and phosphorylates histone H3 in the striatonigral medium spiny neurons of hemiparkinsonian mice. J Neurochem. 2009;108(3):621–33. doi:10.1111/j.1471-4159.2008.05831.x.
Santini E, Sgambato-Faure V, Li Q, Savasta M, Dovero S, Fisone G, Bezard E. Distinct changes in cAMP and extracellular signal-regulated protein kinase signalling in L-DOPA-induced dyskinesia. PLoS One. 2010;5(8):e12322. doi:10.1371/journal.pone.0012322.
Sasaki T, Kotera J, Omori K. Transcriptional activation of phosphodiesterase 7B1 by dopamine D1 receptor stimulation through the cyclic AMP/cyclic AMP-dependent protein kinase/cyclic AMP-response element binding protein pathway in primary striatal neurons. J Neurochem. 2004;89(2):474–83. doi:10.1111/j.1471-4159.2004.02354.x.
Schmidt CJ, Chapin DS, Cianfrogna J, Corman ML, Hajos M, Harms JF, Hoffman WE, Lebel LA, McCarthy SA, Nelson FR, Proulx-LaFrance C, Majchrzak MJ, Ramirez AD, Schmidt K, Seymour PA, Siuciak JA, Tingley FD 3rd, Williams RD, Verhoest PR, Menniti FS. Preclinical characterization of selective phosphodiesterase 10A inhibitors: a new therapeutic approach to the treatment of schizophrenia. J Pharmacol Exp Ther. 2008;325(2):681–90. doi:10.1124/jpet.107.132910.
Seeger TF, Bartlett B, Coskran TM, Culp JS, James LC, Krull DL, Lanfear J, Ryan AM, Schmidt CJ, Strick CA, Varghese AH, Williams RD, Wylie PG, Menniti FS. Immunohistochemical localization of PDE10A in the rat brain. Brain Res. 2003;985(2):113–26.
Seifert R, Schneider EH, Bahre H. From canonical to non-canonical cyclic nucleotides as second messengers: pharmacological implications. Pharmacol Ther. 2015;148:154–84. doi:10.1016/j.pharmthera.2014.12.002.
Shen W, Flajolet M, Greengard P, Surmeier DJ. Dichotomous dopaminergic control of striatal synaptic plasticity. Science. 2008;321(5890):848–51. doi:10.1126/science.1160575.
Shen W, Plotkin JL, Francardo V, Ko WK, Xie Z, Li Q, Fieblinger T, Wess J, Neubig RR, Lindsley CW, Conn PJ, Greengard P, Bezard E, Cenci MA, Surmeier DJ. M4 muscarinic receptor signaling ameliorates striatal plasticity deficits in models of L-DOPA-induced dyskinesia. Neuron. 2015;88(4):762–73. doi:10.1016/j.neuron.2015.10.039.
Siuciak JA, Chapin DS, Harms JF, Lebel LA, McCarthy SA, Chambers L, Shrikhande A, Wong S, Menniti FS, Schmidt CJ. Inhibition of the striatum-enriched phosphodiesterase PDE10A: a novel approach to the treatment of psychosis. Neuropharmacology. 2006a;51(2):386–96. doi:10.1016/j.neuropharm.2006.04.013.
Siuciak JA, McCarthy SA, Chapin DS, Fujiwara RA, James LC, Williams RD, Stock JL, McNeish JD, Strick CA, Menniti FS, Schmidt CJ. Genetic deletion of the striatum-enriched phosphodiesterase PDE10A: evidence for altered striatal function. Neuropharmacology. 2006b;51(2):374–85. doi:10.1016/j.neuropharm.2006.01.012.
Siuciak JA, McCarthy SA, Chapin DS, Reed TM, Vorhees CV, Repaske DR. Behavioral and neurochemical characterization of mice deficient in the phosphodiesterase-1B (PDE1B) enzyme. Neuropharmacology. 2007;53(1):113–24. doi:10.1016/j.neuropharm.2007.04.009.
Solis O, Espadas I, Del-Bel EA, Moratalla R. Nitric oxide synthase inhibition decreases l-DOPA-induced dyskinesia and the expression of striatal molecular markers in Pitx3(−/−) aphakia mice. Neurobiol Dis. 2015;73:49–59. doi:10.1016/j.nbd.2014.09.010.
Stephenson DT, Coskran TM, Wilhelms MB, Adamowicz WO, O'Donnell MM, Muravnick KB, Menniti FS, Kleiman RJ, Morton D. Immunohistochemical localization of phosphodiesterase 2A in multiple mammalian species. J Histochem Cytochem. 2009;57(10):933–49. doi:10.1369/jhc.2009.953471.
Stipanovich A, Valjent E, Matamales M, Nishi A, Ahn JH, Maroteaux M, et al. A phosphatase cascade by which rewarding stimuli control nucleosomal response. Nature. 2008;453(7197):879–84.
Stone JR, Marletta MA. Soluble guanylate cyclase from bovine lung: activation with nitric oxide and carbon monoxide and spectral characterization of the ferrous and ferric states. Biochemistry. 1994;33(18):5636–40.
Strick CA, James LC, Fox CB, Seeger TF, Menniti FS, Schmidt CJ. Alterations in gene regulation following inhibition of the striatum-enriched phosphodiesterase, PDE10A. Neuropharmacology. 2010;58(2):444–51. doi:10.1016/j.neuropharm.2009.09.008.
Sung KW, Choi S, Lovinger DM. Activation of group I mGluRs is necessary for induction of long-term depression at striatal synapses. J Neurophysiol. 2001;86(5):2405–12.
Svenningsson P, Nishi A, Fisone G, Girault JA, Nairn AC, Greengard P. DARPP-32: an integrator of neurotransmission. Annu Rev Pharmacol Toxicol. 2004;44:269–96. doi:10.1146/annurev.pharmtox.44.101802.121415.
Takuma K, Tanaka T, Takahashi T, Hiramatsu N, Ota Y, Ago Y, Matsuda T. Neuronal nitric oxide synthase inhibition attenuates the development of L-DOPA-induced dyskinesia in hemi-Parkinsonian rats. Eur J Pharmacol. 2012;683(1-3):166–73. doi:S0014-2999(12)00248-8 [pii]10.1016/j.ejphar.2012.03.008
Tekumalla PK, Calon F, Rahman Z, Birdi S, Rajput AH, Hornykiewicz O, Di Paolo T, Bédard PJ, Nestler EJ. Elevated levels of DeltaFosB and RGS9 in striatum in Parkinson's disease. Biol Psychiatry. 2001;50(10):813–6. doi:S0006-3223(01)01234-3 [pii]
Threlfell S, West AR. Review: modulation of striatal neuron activity by cyclic nucleotide signaling and phosphodiesterase inhibition. Basal ganglia. 2013;3(3):137–46. doi:10.1016/j.baga.2013.08.001.
Threlfell S, West AR. Role of cyclic nucleotide signaling and phosphodiesterase activation in the modulation of electrophysiological activity of central neurons. In: Brandon NJ, West AR, editors. Cyclic-nucleotide Phosphodiesterases in the central nervous system: from biology to drug discovery. 1st ed. New York: Wiley; 2014. p. 269–302.
Threlfell S, Sammut S, Menniti FS, Schmidt CJ, West AR. Inhibition of phosphodiesterase 10A increases the responsiveness of striatal projection neurons to cortical stimulation. J Pharmacol Exp Ther. 2009;328(3):785–95. doi:jpet.108.146332 [pii]10.1124/jpet.108.146332
Tsou K, Snyder GL, Greengard P. Nitric oxide/cGMP pathway stimulates phosphorylation of DARPP-32, a dopamine- and cAMP-regulated phosphoprotein, in the substantia nigra. Proc Natl Acad Sci U S A. 1993;90(8):3462–5.
Van Staveren WC, Steinbusch HW, Markerink-Van Ittersum M, Repaske DR, Goy MF, Kotera J, Omori K, Beavo JA, De Vente J. mRNA expression patterns of the cGMP-hydrolyzing phosphodiesterases types 2, 5, and 9 during development of the rat brain. J Comp Neurol. 2003;467(4):566–80. doi:10.1002/cne.10955.
Verhoest PR, Proulx-Lafrance C, Corman M, Chenard L, Helal CJ, Hou X, Kleiman R, Liu S, Marr E, Menniti FS, Schmidt CJ, Vanase-Frawley M, Schmidt AW, Williams RD, Nelson FR, Fonseca KR, Liras S. Identification of a brain penetrant PDE9A inhibitor utilizing prospective design and chemical enablement as a rapid lead optimization strategy. J Med Chem. 2009;52(24):7946–9. doi:10.1021/jm9015334.
Wang P, Wu P, Egan RW, Billah MM. Identification and characterization of a new human type 9 cGMP-specific phosphodiesterase splice variant (PDE9A5). Differential tissue distribution and subcellular localization of PDE9A variants. Gene. 2003;314:15–27.
Wang Z, Kai L, Day M, Ronesi J, Yin HH, Ding J, Tkatch T, Lovinger DM, Surmeier DJ. Dopaminergic control of corticostriatal long-term synaptic depression in medium spiny neurons is mediated by cholinergic interneurons. Neuron. 2006;50(3):443–52. doi:10.1016/j.neuron.2006.04.010.
West AR, Galloway MP (1996) Regulation of serotonin-facilitated dopamine release in vivo: the role of protein kinase a activating transduction mechanisms. Synapse 23 (1):20–27. doi:10.1002/(SICI)1098–2396(199605)23:1<20::AID-SYN3>3.0.CO;2-J.
West AR, Grace AA. The nitric oxide-guanylyl cyclase signaling pathway modulates membrane activity states and electrophysiological properties of striatal medium spiny neurons recorded in vivo. J Neurosci. 2004;24(8):1924–35. doi:24/8/1924 [pii]10.1523/JNEUROSCI.4470-03.2004
West AR, Tseng KY. Nitric oxide-soluble Guanylyl cyclase-cyclic GMP signaling in the striatum: new targets for the treatment of Parkinson's disease? Front Syst Neurosci. 2011;5:55. doi:10.3389/fnsys.2011.00055.
West MJ, Ostergaard K, Andreassen OA, Finsen B (1996) Estimation of the number of somatostatin neurons in the striatum: an in situ hybridization study using the optical fractionator method. J Comp Neurol 370 (1):11–22. doi:10.1002/(SICI)1096–9861(19960617)370:1<11::AID-CNE2>3.0.CO;2-O.
West AR, Galloway MP, Grace AA. Regulation of striatal dopamine neurotransmission by nitric oxide: effector pathways and signaling mechanisms. Synapse. 2002;44(4):227–45. doi:10.1002/syn.10076.
Westin JE, Vercammen L, Strome EM, Konradi C, Cenci MA. Spatiotemporal pattern of striatal ERK1/2 phosphorylation in a rat model of L-DOPA-induced dyskinesia and the role of dopamine D1 receptors. Biol Psychiatry. 2007;62(7):800–10. doi:10.1016/j.biopsych.2006.11.032.
Wilson JM, Ogden AM, Loomis S, Gilmour G, Baucum AJ 2nd, Belecky-Adams TL, Merchant KM. Phosphodiesterase 10A inhibitor, MP-10 (PF-2545920), produces greater induction of c-Fos in dopamine D2 neurons than in D1 neurons in the neostriatum. Neuropharmacology. 2015;99:379–86. doi:10.1016/j.neuropharm.2015.08.008.
Xie Z, Adamowicz WO, Eldred WD, Jakowski AB, Kleiman RJ, Morton DG, Stephenson DT, Strick CA, Williams RD, Menniti FS. Cellular and subcellular localization of PDE10A, a striatum-enriched phosphodiesterase. Neuroscience. 2006;139(2):597–607. doi:10.1016/j.neuroscience.2005.12.042.
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Padovan-Neto, F.E., West, A.R. (2017). Regulation of Striatal Neuron Activity by Cyclic Nucleotide Signaling and Phosphodiesterase Inhibition: Implications for the Treatment of Parkinson’s Disease. In: Zhang, HT., Xu, Y., O'Donnell, J. (eds) Phosphodiesterases: CNS Functions and Diseases. Advances in Neurobiology, vol 17. Springer, Cham. https://doi.org/10.1007/978-3-319-58811-7_10
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