Time-dependent involvement of cAMP and cGMP in consolidation of object memory: Studies using selective phosphodiesterase type 2, 4 and 5 inhibitors

Rutten, Kris; Prickaerts, Jos; Hendrix, Martin; Staay, Franz Josef van der; Şık, Ayhan; Blokland, Arjan

doi:10.1016/j.ejphar.2006.11.041

Cited by 166 publications

(179 citation statements)

References 28 publications

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“…102 The PDE4 inhibitors MEM1018 and MEM1091 influence NMDA receptor-dependent memory, 103 and other selective PDE4 inhibitors including rolipram have been shown to influence memory and cognition in several studies. [103][104][105][106][107][108][109][110] Moreover, translation of specific PDE4 isoforms is regulated during long-term potentiation 111 and in NMDA-receptor-mediated memory functions. 112 PDE4s also influence myelination, 113 and rolipram has been shown to reduce demyelination and CNS inflammation, 114 and to promote axon regrowth and myelination in vivo.…”

Section: Pde4b As a Risk Factor For Psychiatric Illness: Interaction mentioning

confidence: 99%

The DISC locus in psychiatric illness

et al. 2007

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The DISC locus is located at the breakpoint of a balanced t(1;11) chromosomal translocation in a large and unique Scottish family. This translocation segregates in a highly statistically significant manner with a broad diagnosis of psychiatric illness, including schizophrenia, bipolar disorder and major depression, as well as with a narrow diagnosis of schizophrenia alone. Two novel genes were identified at this locus and due to the high prevalence of schizophrenia in this family, they were named Disrupted-in-Schizophrenia-1 (DISC1) and Disrupted-in-Schizophrenia-2 (DISC2). DISC1 encodes a novel multifunctional scaffold protein, whereas DISC2 is a putative noncoding RNA gene antisense to DISC1. A number of independent genetic linkage and association studies in diverse populations support the original linkage findings in the Scottish family and genetic evidence now implicates the DISC locus in susceptibility to schizophrenia, schizoaffective disorder, bipolar disorder and major depression as well as various cognitive traits. Despite this, with the exception of the t(1;11) translocation, robust evidence for a functional variant(s) is still lacking and genetic heterogeneity is likely. Of the two genes identified at this locus, DISC1 has been prioritized as the most probable candidate susceptibility gene for psychiatric illness, as its protein sequence is directly disrupted by the translocation. Much research has been undertaken in recent years to elucidate the biological functions of the DISC1 protein and to further our understanding of how it contributes to the pathogenesis of schizophrenia. These data are the main subject of this review; however, the potential involvement of DISC2 in the pathogenesis of psychiatric illness is also discussed. A detailed picture of DISC1 function is now emerging, which encompasses roles in neurodevelopment, cytoskeletal function and cAMP signalling, and several DISC1 interactors have also been defined as independent genetic susceptibility factors for psychiatric illness. DISC1 is a hub protein in a multidimensional risk pathway for major mental illness, and studies of this pathway are opening up opportunities for a better understanding of causality and possible mechanisms of intervention. Molecular Psychiatry (2008) 13, 36-64; doi:10.1038/sj.mp.4002106; published online 2 October 2007 Keywords: schizophrenia; bipolar disorder; depression; DISC1; DISC2; mouse models Genetics of DISC1 discoverySt Clair et al. 1 first reported a Scottish family with a high loading of major mental illness, which cosegregates with a t(1;11) translocation. Long-term follow-up of this family over a period of 30 years has reported 87 family members, of whom 37 carry the translocation. 2 Of 29 individuals carrying the translocation, for whom psychiatric assessment was possible, 7 have a diagnosis of schizophrenia, 1 has a diagnosis of bipolar disorder and 10 cases of recurrent major depression were also reported. 2 Thus, 18 of 29 translocation carriers are diagnosed with major mental illness whereas none of...

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Section: Pde4b As a Risk Factor For Psychiatric Illness: Interaction mentioning

confidence: 99%

The DISC locus in psychiatric illness

et al. 2007

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“…Before testing starts, the animals are often familiarized or habituated and protocols differ greatly between laboratories. In some laboratories the animals are allowed to familiarize with only the apparatus [2,11,12,23], others also introduce objects in the pre-experimental phase [25] or even let the animals undergo the full testing procedure, including injections [34,35]. Even more fundamental, there is no consensus about the definition of object investigation.…”

Section: Introductionmentioning

confidence: 99%

“…Both drugs have proven reliably to attenuate the novel object preference in a 1 h retention delay, likely due to drug induced memory impairment [6,39,40]. 24 h retention intervals were used to investigate drug effects on natural forgetting, as our male Wistar rats normally do not discriminate anymore between the novel and the familiar object after such an interval [1,8,[33][34][35].…”

Section: Introductionmentioning

confidence: 99%

Object recognition testing: Methodological considerations on exploration and discrimination measures

Akkerman

Blokland

Reneerkens

et al. 2012

Behavioural Brain Research

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“…Evidence is accumulating that second messenger molecules, cGMP and cAMP, are important in memory processes in general and long-term potentiation in particular (Bach et al, 1999;Bernabeu et al, 1996;Bourtchouladze et al, 1998;Frey et al, 1993;Lu et al, 1999;Prickaerts et al, 2002a;Son et al, 1998). We have previously shown that PDE4, PDE5, and PDE2 inhibitors all improved the performance of rodents in an object recognition task (ORT) and the timedependent effects of cGMP-or cAMP-selective PDE inhibitors suggested that cGMP was mainly involved in early phase consolidation processes and cAMP in late phase consolidation processes (Rutten et al, 2007b).…”

Section: Introductionmentioning

confidence: 99%

“…PDE inhibitors present a novel therapeutic approach with which to arrest cognitive decline (Gong et al, 2004;Vitolo et al, 2002) or possibly reverse the decline with cognition enhancement Halene and Siegel 2007;Menniti et al, 2006;Rutten et al, 2008). Three promising targets through which memory improvement may be effected are cAMP-selective PDE4 (Barad et al, 1998;Rose et al, 2005;Rutten et al, 2007a;Zhang et al, 2005); cGMP-selective PDE5 (Prickaerts et al, 2004;Rutten et al, 2005); and PDE2, which hydrolyzes both cAMP and cGMP (Boess et al, 2004;Rutten et al, 2007b;Van Donkelaar et al, 2008). Evidence is accumulating that second messenger molecules, cGMP and cAMP, are important in memory processes in general and long-term potentiation in particular (Bach et al, 1999;Bernabeu et al, 1996;Bourtchouladze et al, 1998;Frey et al, 1993;Lu et al, 1999;Prickaerts et al, 2002a;Son et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

Phosphodiesterase Inhibitors Enhance Object Memory Independent of Cerebral Blood Flow and Glucose Utilization in Rats

Rutten

Donkelaar

Ferrington

et al. 2009

Neuropsychopharmacol

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113

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Phosphodiesterase (PDE) inhibitors prevent the breakdown of the second messengers, cyclic AMP (cAMP) and cyclic GMP (cGMP), and are currently studied as possible targets for cognitive enhancement. Earlier studies indicated beneficial effects of PDE inhibitors in object recognition. In this study we tested the effects of three PDE inhibitors on spatial memory as assessed in a place and object recognition task. Furthermore, as both cAMP and cGMP are known vasodilators, the effects of PDE inhibition on cognitive functions could be explained by enhancement of cerebrovascular function. We examined this possibility by measuring the effects of PDE5 and PDE4 inhibitor treatment on local cerebral blood flow and glucose utilization in rats using [ 14 C]-iodoantipyrine and [ 14 C]-2-deoxyglucose quantitative autoradiography, respectively. In the spatial location task, PDE5 inhibition (cGMP) with vardenafil enhanced only early phase consolidation, PDE4 inhibition (cAMP) with rolipram enhanced only late phase consolidation, and PDE2 inhibition (cAMP and cGMP) with Bay 60-7550 enhanced both consolidation processes. Furthermore, PDE5 inhibition had no cerebrovascular effects in hippocampal or rhinal areas. PDE4 inhibition increased rhinal, but not hippocampal blood flow, whereas it decreased glucose utilization in both areas. In general, PDE5 inhibition decreased the ratio between blood flow and glucose utilization, indicative of general oligaemia; whereas PDE4 inhibition increased this ratio, indicative of general hyperemia. Both oligaemic and hyperemic conditions are detrimental for brain function and do not explain memory enhancement. These results underscore the specific effects of cAMP and cGMP on memory consolidation (object and spatial memory) and provide evidence that the underlying mechanisms of PDE inhibition on cognition are independent of cerebrovascular effects.

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Time-dependent involvement of cAMP and cGMP in consolidation of object memory: Studies using selective phosphodiesterase type 2, 4 and 5 inhibitors

Cited by 166 publications

References 28 publications

The DISC locus in psychiatric illness

The DISC locus in psychiatric illness

Object recognition testing: Methodological considerations on exploration and discrimination measures

Phosphodiesterase Inhibitors Enhance Object Memory Independent of Cerebral Blood Flow and Glucose Utilization in Rats

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