Molecular Psychology: Roles for the ERK MAP Kinase Cascade in Memory

Adams, J. Paige; Sweatt, J. David

doi:10.1146/annurev.pharmtox.42.082701.145401

Cited by 548 publications

(409 citation statements)

References 146 publications

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“…Recent studies have shown that inhibition of hippocampal MEK/ERK signaling impairs synaptic plasticity as well as long-term memory formation (Davis et al, 2000;Kelly et al, 2003;Adams and Sweatt, 2002). Consistent with this, in the present study, direct infusion of U0126, a specific MEK inhibitor (Hotokezaka et al, 2002), into the CA1 subregion of the hippocampus, also impaired reference memory in the Rats were treated with U0126 and rolipram 24 h after initial training; test data shown were obtained 24 and 48 h posttraining.…”

Section: Discussionsupporting

confidence: 90%

“…Inhibition of cAMP/PKA signaling impairs memory, especially long-term memory (Koh et al, 2002); stimulation of this pathway enhances memory (Barad et al, 1998;. Similar to cAMP signaling, the MEK/mitogen-activated protein kinase (MAPK, ERK) pathway also has been shown to be involved in the mediation of synaptic plasticity and memory (Adams and Sweatt, 2002;Schafe et al, 2000;Sharma et al, 2003). Activation of ERK signaling enhances the induction of longterm-synaptic facilitation as well as long-term memory (Purcell et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of the Phosphodiesterase 4 (PDE4) Enzyme Reverses Memory Deficits Produced by Infusion of the MEK Inhibitor U0126 into the CA1 Subregion of the Rat Hippocampus

Zhang

Zhao

Huang

et al. 2004

Neuropsychopharmacol

134

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Cyclic AMP-specific phosphodiesterase 4 (PDE4), which is an integral component of NMDA receptor-mediated cAMP signaling, is involved in the mediation of memory processes. Given that NMDA receptors also mediate MEK/mitogen-activated protein kinase (MAPK, ERK) signaling, which is involved in synaptic plasticity, and that some PDE4 subtypes are phosphorylated and regulated by ERK, it was of interest to determine if PDE4 is involved in MEK/ERK signaling-mediated memory. It was found that rolipram, a PDE4-selective inhibitor, reversed the amnesic effect in the radial-arm maze test of the MEK inhibitor U0126 administered into the CA1 subregion of the rat hippocampus. Consistent with this, rolipram, either by peripheral administration or direct intra-CA1 infusion, enhanced the retrieval of long-term memory impaired by intra-CA1 infusion of U0126 using the step-through inhibitory avoidance test. The same dose of rolipram did not affect U0126-induced reduction of phospho-ERK1/2 levels in the CA1 subregion. However, in primary cultures of rat cerebral cortical neurons, pretreatment with U0126 increased PDE4 activity; this was correlated with the U0126-induced reduction of phospho-ERK1/2 levels. These results suggest that MEK/ERK signaling plays an inhibitory role in regulating PDE4 activity in the brain; this may be a novel mechanism by which MEK/ERK signaling mediates memory. PDE4 is likely to be an important link between the cAMP/PKA and MEK/ERK signaling pathways in the mediation of memory.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Inhibition of the Phosphodiesterase 4 (PDE4) Enzyme Reverses Memory Deficits Produced by Infusion of the MEK Inhibitor U0126 into the CA1 Subregion of the Rat Hippocampus

Zhang

Zhao

Huang

et al. 2004

Neuropsychopharmacol

134

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“…The Ras-controlled Raf-MEK-ERK protein kinase signaling cascade is known to play a critical role in the development of neuronal plasticity Sweatt, 1996, 1997;Martin et al, 1997) and long-term memory formation (Atkins et al, 1998;Orban et al, 1999;Adams and Sweatt, 2002). Changes in ERK signaling have also been associated with drug-dependent behavioral plasticity (Pierce et al, 1999;Valjent et al, 2000;Mazzucchelli et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

“…For example, pharmacological inhibition of MEK, the upstream activator of the two major ERK isoforms in the brain (ERK1 and ERK2), prevents both hippocampus-and amygdala-dependent memory formation (Atkins et al, 1998;Schafe et al, 1999;Adams and Sweatt, 2002). Pharmacological blockade of the Raf-MEK-ERK cascade also attenuates the development of a conditioned place preference to cocaine, amphetamine or MDMA (Valjent et al, 2000;Salzmann et al, 2003;Gerdjikov et al, 2004) and appears to modulate the development of psychomotor sensitization to cocaine (Pierce et al, 1999;Valjent et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Knockout of ERK1 Enhances Cocaine-Evoked Immediate Early Gene Expression and Behavioral Plasticity

Ferguson

Fasano

Yang

et al. 2006

Neuropsychopharmacol

110

100

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The ability of cocaine to produce lasting neural adaptations in mesocorticolimbic brain regions is thought to promote drug seeking and facilitate addiction in humans. The Ras-controlled Raf-MEK-ERK protein kinase signaling cascade has been implicated in the behavioral and neurobiological actions of cocaine in animals. However, these pharmacological studies have not been able to determine the specific role of the two predominant isoforms of ERK (ERK1 and ERK2) in these processes. We report here that deletion of the ERK1 isoform, which leads to increased ERK2 stimulus-dependent signaling, facilitates the development of cocaine-induced psychomotor sensitization and the acquisition of a cocaine conditioned place preference. Conversely, pharmacological blockade of ERK signaling attenuates the development of psychomotor sensitization to cocaine. Finally, cocaine-evoked gene expression in mesocorticolimbic brain regions is potentiated in ERK1-deficient mice. Thus, alterations in ERK signaling influence both the neurobiological impact of cocaine and its ability to produce enduring forms of drug experience-dependent behavioral plasticity. Our results suggest that enhanced ERK2 signaling following repeated drug exposure may facilitate the development of forms of cocaine-induced plasticity that contribute to addiction.

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“…32 Thinking along these lines, improvement in cognition and in learning processes has been closely related to activation of MAP kinases. 60 These second messengers, in turn, are known to be stimulated by EPO in neurons. 27,[61][62][63] Another novel finding was the effect of EPO treatment on serum levels of the glial damage marker, S100B.…”

Section: H Ehrenreich Et Almentioning

confidence: 99%

Improvement of cognitive functions in chronic schizophrenic patients by recombinant human erythropoietin

et al. 2006

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Schizophrenia is increasingly recognized as a neurodevelopmental disease with an additional degenerative component, comprising cognitive decline and loss of cortical gray matter. We hypothesized that a neuroprotective/neurotrophic add-on strategy, recombinant human erythropoietin (rhEPO) in addition to stable antipsychotic medication, may be able to improve cognitive function even in chronic schizophrenic patients. Therefore, we designed a doubleblind, placebo-controlled, randomized, multicenter, proof-of-principle (phase II) study. This study had a total duration of 2 years and an individual duration of 12 weeks with an additional safety visit at 16 weeks. Chronic schizophrenic men (N = 39) with defined cognitive deficit (X1 s.d. below normal in the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)), stable medication and disease state, were treated for 3 months with a weekly short (15 min) intravenous infusion of 40 000 IU rhEPO (N = 20) or placebo (N = 19). Main outcome measure was schizophrenia-relevant cognitive function at week 12. The neuropsychological test set (RBANS subtests delayed memory, language-semantic fluency, attention and Wisconsin Card Sorting Test (WCST-64) -perseverative errors) was applied over 2 days at baseline, 2 weeks, 4 weeks and 12 weeks of study participation. Both placebo and rhEPO patients improved in all evaluated categories. Patients receiving rhEPO showed a significant improvement over placebo patients in schizophrenia-related cognitive performance (RBANS subtests, WCST-64), but no effects on psychopathology or social functioning. Also, a significant decline in serum levels of S100B, a glial damage marker, occurred upon rhEPO. The fact that rhEPO is the first compound to exert a selective and lasting beneficial effect on cognition should encourage new treatment strategies for schizophrenia.

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Molecular Psychology: Roles for the ERK MAP Kinase Cascade in Memory

Cited by 548 publications

References 146 publications

Inhibition of the Phosphodiesterase 4 (PDE4) Enzyme Reverses Memory Deficits Produced by Infusion of the MEK Inhibitor U0126 into the CA1 Subregion of the Rat Hippocampus

Inhibition of the Phosphodiesterase 4 (PDE4) Enzyme Reverses Memory Deficits Produced by Infusion of the MEK Inhibitor U0126 into the CA1 Subregion of the Rat Hippocampus

Knockout of ERK1 Enhances Cocaine-Evoked Immediate Early Gene Expression and Behavioral Plasticity

Improvement of cognitive functions in chronic schizophrenic patients by recombinant human erythropoietin

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