Regionally Specific Regulation of ERK MAP Kinase in a Model of Antidepressant-Sensitive Chronic Depression

Gourley, Shannon L.; Wu, Florence J.; Kiraly, Drew D.; Ploski, Jonathan E.; Kedves, Alexia T.; Duman, Ronald S.; Taylor, Jane R.

doi:10.1016/j.biopsych.2007.07.016

Cited by 251 publications

(238 citation statements)

References 49 publications

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“…In Bdnf ϩ/Ϫ mice, independent groups were used for devaluation and PR tests. Breakpoint ratios Ͼ2 SDs outside of the group means were excluded (Gourley et al, 2008a; throughout all experiments: n ϭ 1 lenti-GFP; n ϭ 3 intact wild-type; n ϭ 1 Bdnf ϩ/Ϫ plus vehicle; n ϭ 2 Bdnf ϩ/Ϫ plus BDNF. Additionally, two Bdnf knockdown mice were excluded because of experimenter error.…”

Section: Pr Testmentioning

confidence: 99%

“…The scalp was incised, skin retracted, and bregma and lambda identified. The head was leveled, and recombinant human BDNF (Millipore Bioscience Research Reagents) dissolved in saline (0.4 g/l; Gourley et al, 2008bGourley et al, , 2009aGourley et al, , 2012 was infused into the mOFC (ϩ2.3 mm AP, Ϫ2.8 mm DV, Ϯ0.1 mm ML; Gourley et al, 2010) in a volume of 0.2 l over 6 min using a digital coordinate system with 1 ⁄100 mm resolution (David Kopf Instruments).…”

Section: Bdnf Microinfusionmentioning

confidence: 99%

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The Medial Orbitofrontal Cortex Regulates Sensitivity to Outcome Value

et al. 2016

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An essential component of goal-directed decision-making is the ability to maintain flexible responding based on the value of a given reward, or "reinforcer." The medial orbitofrontal cortex (mOFC), a subregion of the ventromedial prefrontal cortex, is uniquely positioned to regulate this process. We trained mice to nose poke for food reinforcers and then stimulated this region using CaMKII-driven G s -coupled designer receptors exclusively activated by designer drugs (DREADDs). In other mice, we silenced the neuroplasticityassociated neurotrophin brain-derived neurotrophic factor (BDNF). Activation of G s -DREADDs increased behavioral sensitivity to reinforcer devaluation, whereas Bdnf knockdown blocked sensitivity. These changes were accompanied by modifications in breakpoint ratios in a progressive ratio task, and they were recapitulated in Bdnf ϩ/Ϫ mice. Replacement of BDNF selectively in the mOFC in Bdnf ϩ/Ϫ mice rescued behavioral deficiencies, as well as phosphorylation of extracellular-signal regulated kinase 1/2 (ERK1/2). Thus, BDNF expression in the mOFC is both necessary and sufficient for the expression of typical effort allocation relative to an anticipated reinforcer. Additional experiments indicated that expression of the immediate-early gene c-fos was aberrantly elevated in the Bdnf ϩ/Ϫ dorsal striatum, and BDNF replacement in the mOFC normalized expression. Also, systemic administration of an MAP kinase kinase inhibitor increased breakpoint ratios, whereas the addition of discrete cues bridging the response-outcome contingency rescued breakpoints in Bdnf ϩ/Ϫ mice. We argue that BDNF-ERK1/2 in the mOFC is a key regulator of "online" goal-directed action selection.

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Section: Pr Testmentioning

confidence: 99%

Section: Bdnf Microinfusionmentioning

confidence: 99%

The Medial Orbitofrontal Cortex Regulates Sensitivity to Outcome Value

et al. 2016

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“…In order to avoid this issue, several groups used exogenously applied corticosterone to induce anxiety-like behavior [18,51−53], since corticosterone is an adrenal hormone which is produced when the individual is under stressful situations such as restraint stress and exposure to predator. The dysfunction of the HPA-axis and hypercortisolemia found in depressive patients also support the application of corticosterone to simulate depressive/anxious state in animals [54,55]. In short, various animal models were used to study anxiety-like behavior and this may be one of the causes of inconsistent findings across different studies.…”

Section: Neurogenesis and Anxiety Disordersmentioning

confidence: 83%

Neurogenic hypothesis and psychiatric disorders

Lau

Lee

2013

Chin. Sci. Bull.

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Psychiatric illness, such as affective disorders, anxiety disorders and schizophrenia, exerts exceptional personal burden on affected individuals. Although not physically noticeable, these disorders cost enormously on ones' family and society. Currently pharmaceutical and psychological treatments are generally accepted as effective for psychiatric disorders, while the exact mechanisms underlying the treatment efficacy, etiology and neurobiology of the disorders remain elusive. In the past decade, "neurogenic hypothesis" emerged as an attempt to explain the nature of psychiatric illness. The origination of the hypothesis is based on several pre-clinical and clinical observations. First, stress, which is a common risk factor of the disorders, was found to suppress neurogenesis; second, treatment for the illnesses like antidepressants and antipsychotics were shown to improve neurogenesis and behavioral deficits simultaneously; and third, the therapeutic effect of antidepressants was abolished in animal models when neurogenesis was blocked. Increasing efforts were invested to determine whether neurogenesis is a key to the understanding and treatment of psychiatric disorders, although contrasting results are also found and thus the importance of neurogenesis remains a matter of debate. The present chapter will discuss the recent findings about the involvement of neurogenesis in major depression, anxiety disorders and schizophrenia, and whether neurogenesis would be a potential target for development of the treatment in the future.neurogenesis, psychiatric disorders, major depression, schizophrenia, anxiety disorder, hippocampus, amygdala, subventricular zone Citation:

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“…It has been indicated that inhibition of MAPK produces a depressive phenotype and blocks behavioral effects of antidepressants. ERK including ERK1 and ERK2 belongs to the MAPKs family, and accumulating evidences suggest that ERK signal path way may take part in pathogenesis of depression and the mechanism of antidepressant-like action (Gourley et al, 2008). ERK is one of the most-studied intracellular signaling pathways and it is highly sensitive to stress and closely associated with mood processing (Gerrits et al, 2006;Rubinfeld and Seger, 2005).…”

Section: Discussionmentioning

confidence: 99%

“…3.8 PSY increased the phosphorylation of CREB and ERK in the hippocampus of rats CREB is an important transcription factor for BDNF in hippocampus, and it has also been involved in the actions of antidepressants (Lane-Ladd et al, 1997).The ERK is another key signal pathway of BDNF, and the phosphorylation of both CREB and ERK1/2 has been proposed as an intracellular common mechanism of antidepressant (Gourley et al, 2008). Therefore, we examined the phosphorylation of CREB and ERK among the treatment groups in the hippocampus, the phosphorylation of CREB and ERK being expressed as a ratio of the pCREB/CREB and pERK/ERK.…”

Section: Psy Treatment Reverses the Cums-induced Depressive Behavior mentioning

confidence: 99%

Piper sarmentosum Roxb. produces antidepressant-like effects in rodents, associated with activation of the CREB-BDNF-ERK signaling pathway and reversal of HPA axis hyperactivity

Gao

et al. 2017

Journal of Ethnopharmacology

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Ethnopharmacological relevance: There are many plants of genus Piper which have been reported to induce antidepressant-like effects, Piper sarmentosum (PS) is one of them. PS is a Chinese herbal medicine and a traditional edible vegetable. Materials and Methods:In the present study, the antidepressant-like effects of PS extracts and the ethyl acetate fraction of PS extracts (PSY) were assessed using the open field test (OFT), forced swimming test (FST), and tail suspension test (TST) in mice. Furthermore, we applied a 4 consecutive weeks of chronic unpredictable mild stress (CUMS) as a model of depression in rats, followed by a sucrose preference test. Then we examined the possible mechanisms of this action.The activity of the hypothalamic-pituitary-adrenal (HPA) axis was evaluated by detecting the serum corticosterone (CORT) concentrations, and the protein expression levels of brain-derived neurotrophic factor (BDNF), the phosphorylated form CREB and ERK1/2 were detected by qRT-PCR or Western blot. Results:The results showed that PS extracts (100, 200 mg/kg) and PSY (12.5, 25, 50 mg/kg) treatment produced antidepressant-like effects in mice similar to fluoxetine (20 mg/kg), indicated by the reduced immobility time in the FST and TST, while both had no influence on the locomotor activity in the OFT. PSY treatment significantly increased sucrose preference and reduced serum CORT levels in CUMS rats. Moreover, PSY up-regulated BDNF protein levels, and increased CREB and ERK phosphorylation levels in the hippocampus on CUMS rats. Conclusions:These findings suggest that the antidepressant-like effects of PS extracts and PSY are mediated, at least in part, by modulating HPA axis, BDNF, CREB and ERK phosphorylation and expression in the hippocampus.

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Regionally Specific Regulation of ERK MAP Kinase in a Model of Antidepressant-Sensitive Chronic Depression

Abstract: Antidepressant efficacy in a motivational task and behavioral despair assay are associated with altered limbic pERK1/2, including restored pERK1/2 in the dentate gyrus after stress-related insult.

Cited by 251 publications

References 49 publications

The Medial Orbitofrontal Cortex Regulates Sensitivity to Outcome Value

The Medial Orbitofrontal Cortex Regulates Sensitivity to Outcome Value

Neurogenic hypothesis and psychiatric disorders

Piper sarmentosum Roxb. produces antidepressant-like effects in rodents, associated with activation of the CREB-BDNF-ERK signaling pathway and reversal of HPA axis hyperactivity

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