Effects of ketamine administration on the phosphorylation levels of CREB and TrKB and on oxidative damage after infusion of MEK inhibitor

Réus, Gislaine Z.; Abaleira, Helena M.; Titus, Stephanie E.; Arent, Camila O.; Michels, Monique; Luz, Jaine R. da; Santos, Maria Augusta B Dos; Carlessi, Anelise S.; Matias, Beatriz I.; Bruchchen, Livia; Steckert, Amanda V.; Ceretta, Luciane Bisognin; Dal‐Pizzol, Felipe; Quevedo, Joao L De

doi:10.1016/j.pharep.2015.08.010

Cited by 21 publications

(20 citation statements)

References 69 publications

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“…Furthermore, postmortem studies indicate that CREB levels are increased in subjects taking antidepressants at the time of death ( (Réus et al, 2015). In agreement with that, in our present study the red wine extract significantly increased the ratio of pCREB/CREB in the hippocampus and prefrontal cortex.…”

Section: Discussionsupporting

confidence: 93%

Antidepressant-like activity of red wine phenolic extracts in repeated corticosterone-induced depression mice via BDNF/TrkB/CREB signaling pathway

et al. 2016

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Abstract. The aim of this study was to investigate the antidepressant-like effect of red wine phenolic extracts in mouse model exposed to exogenous corticosterone. The results showed that 3-week corticosterone injections caused depression-like behavior in mice, as indicated by the significant decrease in sucrose consumption and increase immobility time in the forced swim test. Red wine phenolic extracts treatment significantly reduced serum corticosterone levels. Moreover, it was found that red wine phenolic extract increased the brain-derived neurotrophic factor protein (BNDF) and Tropomyosin-related kinase B (TrkB) phosphorylation and cAMP-responsive element binding protein (CREB) phosphorylation levels in the hippocampus and prefrontal cortex. However, K252a, an inhibitor of TrkB, completely abolished those antidepressant-like effects. These results suggested that the red wine phenolic extracts produce an antidepressant-like effect in corticosterone-treated mice, at least in part, which is possibly mediated by modulating hypothalamic-pituitary-adrenal (HPA) axis, BDNF, TrkB and CREB phosphorylation levels in the brain region of mice.

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Section: Discussionsupporting

confidence: 93%

Antidepressant-like activity of red wine phenolic extracts in repeated corticosterone-induced depression mice via BDNF/TrkB/CREB signaling pathway

et al. 2016

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“…Our data show that acute intrahippocampal infusion of TLQP-62 produces a rapid antidepressant effect in the FST within 30 min, which parallels the time course of ketamine treatment in animal studies 20 , 54 . BDNF/TrkB signaling in hippocampus 54 is required for the rapid antidepressant efficacy of ketamine, and acute ketamine treatment induces the translation of BDNF 54 and TrkB phosphorylation 61 . Here we demonstrate a dependence of TLQP-62 antidepressant actions on BDNF and its signaling pathways in vivo , as noted previously in hippocampal slices, in vitro , where TLQP-62 treatment stimulated electrical excitability that was blocked by the BDNF scavenger TrkB-Fc 16 .…”

Section: Discussionmentioning

confidence: 99%

VGF function in depression and antidepressant efficacy

et al. 2017

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Brain-derived neurotrophic factor (BDNF) is a critical effector of depression-like behavior and antidepressant responses. Here, we show that VGF (non-acronymic), which is robustly regulated by BDNF/TrkB signaling, is downregulated in dorsal hippocampus (dHc) (male/female) and upregulated in nucleus accumbens (NAc) (male) in depressed human subjects and in mice subjected to chronic social defeat stress (CSDS). Adeno-associated virus (AAV)-Cre-mediated Vgf ablation in floxed VGF mice, in dHc or NAc, led to pro-depressant or antidepressant behaviors, respectively, while dHc or NAc AAV-VGF overexpression induced opposite outcomes. Mice with reduced VGF levels in the germline (Vgf+/−) or in dHc (AAV-Cre-injected floxed mice) showed increased susceptibility to CSDS and impaired responses to ketamine treatment in the forced swim test. Floxed mice with conditional pan-neuronal (Synapsin-Cre) but not those with forebrain (αCaMKII-Cre) Vgf ablation displayed increased susceptibility to subthreshold social defeat stress, suggesting that neuronal VGF, expressed in part in inhibitory interneurons, regulates depression-like behavior. Acute antibody-mediated sequestration of VGF-derived C-terminal peptides AQEE-30 and TLQP-62 in dHc induced pro-depressant effects. Conversely, dHc TLQP-62 infusion had rapid antidepressant efficacy, which was reduced in BDNF floxed mice injected in dHc with AAV-Cre, and in NBQX- and rapamycin-pretreated wildtype mice, these compounds blocking α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor and mammalian target of rapamycin (mTOR) signaling, respectively. VGF is therefore a critical modulator of depression-like behaviors in dHc and NAc. In hippocampus, the antidepressant response to ketamine is associated with rapid VGF translation, is impaired by reduced VGF expression, and as previously reported, requires coincident, rapid BDNF translation and release.

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“…Prolonged ketamine exposure in neonates at anesthetic doses has been reported to cause long-term impairments of learning and memory [20]. Furthermore, ketamine decreased p-CREB in the hippocampus [21, 22], and decreased levels of BDNF [23]. CREB has been demonstrated to be involved in learning and memory deficits caused by ketamine [10, 22].…”

Section: Discussionmentioning

confidence: 99%

Ketamine administered pregnant rats impair learning and memory in offspring via the CREB pathway

Guo

et al. 2017

Oncotarget

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Ketamine has been reported to impair the capacity for learning and memory. This study examined whether these capacities were also altered in the offspring and investigated the role of the CREB signaling pathway in pregnant rats, subjected to ketamine-induced anesthesia. On the 14th day of gestation (P14), female rats were anesthetized for 3 h via intravenous ketamine injection (200 mg/Kg). Morris water maze task, contextual and cued fear conditioning, and olfactory tasks were executed between the 25th to 30th day after birth (B25-30) on rat pups, and rats were sacrificed on B30. Nerve density and dendritic spine density were examined via Nissl’s and Golgi staining. Simultaneously, the contents of Ca2+/Calmodulin-Dependent Protein Kinase II (CaMKII), p-CaMKII, CaMKIV, p-CaMKIV, Extracellular Regulated Protein Kinases (ERK), p-ERK, Protein Kinase A (PKA), p-PKA, cAMP-Response Element Binding Protein (CREB), p-CREB, and Brain Derived Neurotrophic Factor (BDNF) were detected in the hippocampus. We pretreated PC12 cells with both PKA inhibitor (H89) and ERK inhibitor (SCH772984), thus detecting levels of ERK, p-ERK, PKA, p-PKA, p-CREB, and BDNF. The results revealed that ketamine impaired the learning ability and spatial as well as conditioned memory in the offspring, and significantly decreased the protein levels of ERK, p-ERK, PKA, p-PKA, p-CREB, and BDNF. We found that ERK and PKA (but not CaMKII or CaMKIV) have the ability to regulate the CREB-BDNF pathway during ketamine-induced anesthesia in pregnant rats. Furthermore, ERK and PKA are mutually compensatory for the regulation of the CREB-BDNF pathway.

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Effects of ketamine administration on the phosphorylation levels of CREB and TrKB and on oxidative damage after infusion of MEK inhibitor

Abstract: Ketamine's effects on pCREB, pTrKB, and oxidative stress are mediated, at least in part, by a mechanism dependent of MAPK signaling inhibition.

Cited by 21 publications

References 69 publications

Antidepressant-like activity of red wine phenolic extracts in repeated corticosterone-induced depression mice via BDNF/TrkB/CREB signaling pathway

Antidepressant-like activity of red wine phenolic extracts in repeated corticosterone-induced depression mice via BDNF/TrkB/CREB signaling pathway

VGF function in depression and antidepressant efficacy

Ketamine administered pregnant rats impair learning and memory in offspring via the CREB pathway

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