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https://www.readbyqxmd.com/read/29742620/ketamine-differentially-restores-diverse-alterations-of-neuroligins-in-brain-regions-in-a-rat-model-of-neuropathic-pain-induced-depression
#1
Wei Pan, Guang-Fen Zhang, Hui-Hui Li, Mu-Huo Ji, Zhi-Qiang Zhou, Kuan-Yu Li, Jian-Jun Yang
Depression is present in a large proportion of patients suffering from chronic pain, and yet the underlying mechanisms remain to be elucidated. Neuroligins (NLs), as a family of cell-adhesion proteins, are involved in synaptic formation and have been linked to various neuropsychiatric disorders. Here, we studied the alterations in NL1 and NL2 in the medial prefrontal cortex (mPFC), the anterior cingulate cortex (ACC), and the hippocampus in a rat model of neuropathic pain-induced depression, and whether ketamine, a rapid and robust antidepressant, could restore these abnormalities...
May 8, 2018: Neuroreport
https://www.readbyqxmd.com/read/29736744/antidepressant-efficacy-and-tolerability-of-ketamine-and-esketamine-a-critical-review
#2
REVIEW
P Molero, J A Ramos-Quiroga, R Martin-Santos, E Calvo-Sánchez, L Gutiérrez-Rojas, J J Meana
Ketamine and its enantiomer S-ketamine (esketamine) are promising candidates to produce a rapid-onset antidepressant effect in treatment-resistant depression. Ketamine causes continued blockade of the glutamate N-methyl-D-aspartate (NMDA) receptor, though this might not primarily mediate the antidepressant effect. Alternative hypotheses include selectivity for the NMDA receptor subtype containing the NMDA receptor subunit 2B (NR2B), inhibition of the phosphorylation of the eukaryotic elongation factor 2 (eEF2) kinase, increased expression of brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrKB), and activation of the mammalian target of rapamycin (mTOR) signaling pathway, alongside other independent actions attributed to the ketamine metabolism to R-hydroxynorketamine (R-HNK)...
May 7, 2018: CNS Drugs
https://www.readbyqxmd.com/read/29673146/predictors-of-response-to-ketamine-in-treatment-resistant-major-depressive-disorder-and-bipolar-disorder
#3
Carola Rong, Caroline Park, Joshua D Rosenblat, Mehala Subramaniapillai, Hannah Zuckerman, Dominika Fus, Yena L Lee, Zihang Pan, Elisa Brietzke, Rodrigo B Mansur, Danielle S Cha, Leanna M W Lui, Roger S McIntyre
OBJECTIVES: Extant evidence indicates that ketamine exerts rapid antidepressant effects in treatment-resistant depressive (TRD) symptoms as a part of major depressive disorder (MDD) and bipolar disorder (BD). The identification of depressed sub-populations that are more likely to benefit from ketamine treatment remains a priority. In keeping with this view, the present narrative review aims to identify the pretreatment predictors of response to ketamine in TRD as part of MDD and BD. METHOD: Electronic search engines PubMed/MEDLINE, ClinicalTrials...
April 17, 2018: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/29596995/applying-ketamine-to-alleviate-the-ptsd-like-effects-by-regulating-the-hcn1-related-bdnf
#4
Lanwei Hou, Yirui Qi, Hongwei Sun, Gang Wang, Qi Li, Yanyu Wang, Zuoji Zhang, Zhongde Du, Lin Sun
BACKGROUND: Post-traumatic stress disorder (PTSD) is commonly associated with concurrent anxiety and depression symptoms, and reduce the expression of the Brain-Derived Neurotrophic Factor (BDNF) which promotes the proliferation and survival of neurons. The hyperpolarization-activated cyclic nucleotide-gated channel 1(HCN1) could be inhibited by the ketamine, a drug to alleviate depression and anxiety, and regulated the BDNF expression, however, the effects of ketamine in alleviating PTSD symptoms by regulating the HCN1-related BDNF have been poorly perceived...
March 26, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/29576706/rhynchophylline-downregulates-phosphorylated-camp-response-element-binding-protein-nuclear-receptor-related-1-and-brain-derived-neurotrophic-factor-expression-in-the-hippocampus-of-ketamine-induced-conditioned-place-preference-rats
#5
Youli Guo, Chaohua Luo, Genghong Tu, Chan Li, Yi Liu, Wei Liu, Ken Kin Lam Yung, Zhixian Mo
Background: Addiction to ketamine is becoming a serious public health issues, for which there exists no effective treatment. Rhynchophylline (Rhy) is an alkaloid extracted from certain Uncaria species that is well known for both its potent anti-addictive and neuroprotective properties. Increasing evidence supports the contributions of cAMP response element binding protein (CREB), nuclear receptor-related-1 (Nurr1), and brain-derived neurotrophic factor (BDNF) in modulating neural and behavioral plasticity which was induced by addictive drugs...
January 2018: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/29559371/intravenous-infusion-of-xenon-containing-liposomes-generates-rapid-antidepressant-like-effects
#6
Manoj P Dandekar, Tao Peng, David D McPherson, Joao Quevedo, Jair C Soares, Shaoling Huang
AIM: Similar to ketamine, xenon gas acts as a glutamatergic N-methyl-d -aspartate receptor antagonist, but devoid of propensity to cause untoward effects. Herein, we loaded xenon gas into a liposomal carrier called xenon-containing liposomes (Xe-liposome) for systemic delivery, and investigated its effect as an antidepressant and also analyzed synaptic biomarkers including brain-derived neurotrophic factor (BDNF), protein kinase B (AKT), mammalian target of rapamycin (mTOR), protein kinase C (PKC) and extracellular signal-regulated kinase-1/2 (ERK1/2) in blood and brain...
March 17, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/29548911/involvement-of-gabaergic-bdnf-and-nox-2-mechanisms-in-the-prevention-and-reversal-of-ketamine-induced-schizophrenia-like-behavior-by-morin-in-mice
#7
Benneth Ben-Azu, Adegbuyi Oladele Aderibigbe, Abayomi Mayowa Ajayi, Aya-Ebi Okubo Eneni, Solomon Umukoro, Ezekiel O Iwalewa
GABAergic (Gamma-aminobutyric acid) and neurotrophic derangements have important implication in schizophrenia, a neuropsychiatric disease. Previous studies have shown that nicotinamide adenine dinucleotide phosphate oxidase (NADPH-oxidase) alters GABAergic and neurotrophic activities via inflammatory and oxidative pathways. Thus, it has been proposed that agents with anti-oxidant and anti-inflammatory properties might be beneficial for the treatment of the disease. Morin is neuroactive bioflavonoid compound, which has been reported to demonstrate antipsychotic and anti-oxidant/anti-inflammatory activities...
March 13, 2018: Brain Research Bulletin
https://www.readbyqxmd.com/read/29532791/mechanisms-of-ketamine-action-as-an-antidepressant
#8
P Zanos, T D Gould
Clinical studies have demonstrated that a single sub-anesthetic dose of the dissociative anesthetic ketamine induces rapid and sustained antidepressant actions. Although this finding has been met with enthusiasm, ketamine's widespread use is limited by its abuse potential and dissociative properties. Recent preclinical research has focused on unraveling the molecular mechanisms underlying the antidepressant actions of ketamine in an effort to develop novel pharmacotherapies, which will mimic ketamine's antidepressant actions but lack its undesirable effects...
March 13, 2018: Molecular Psychiatry
https://www.readbyqxmd.com/read/29516301/convergent-mechanisms-underlying-rapid-antidepressant-action
#9
REVIEW
Panos Zanos, Scott M Thompson, Ronald S Duman, Carlos A Zarate, Todd D Gould
Traditional pharmacological treatments for depression have a delayed therapeutic onset, ranging from several weeks to months, and there is a high percentage of individuals who never respond to treatment. In contrast, ketamine produces rapid-onset antidepressant, anti-suicidal, and anti-anhedonic actions following a single administration to patients with depression. Proposed mechanisms of the antidepressant action of ketamine include N-methyl-D-aspartate receptor (NMDAR) modulation, gamma aminobutyric acid (GABA)-ergic interneuron disinhibition, and direct actions of its hydroxynorketamine (HNK) metabolites...
March 2018: CNS Drugs
https://www.readbyqxmd.com/read/29476799/effects-of-rhynchophylline-on-the-hippocampal-mirna-expression-profile-in-ketamine-addicted-rats
#10
Chan Li, Genghong Tu, Chaohua Luo, Youli Guo, Miao Fang, Chen Zhu, Hancheng Li, Jinying Ou, Yuting Zhou, Wei Liu, Ken Kin Lam Yung, Zhixian Mo
In the past few years, ketamine, a noncompetitive NMDA antagonist, has been widely abused worldwide as a new type of synthetic drug, severely affecting the physical and mental health of ketamine abusers. Previous studies have suggested that rhynchophylline can alleviate drug abuse and reverse the conditioned place preference caused by the abuse. MicroRNAs (miRNAs) are important factors regulating gene expression and are involved in the drug addiction process. The hippocampus is a critical area in the brain involved in causing drug addiction...
February 22, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/29322484/acute-low-dose-ketamine-produces-a-rapid-and-robust-increase-in-plasma-bdnf-without-altering-brain-bdnf-concentrations
#11
Martin Le Nedelec, Paul Glue, Helen Winter, Chelsea Goulton, Lucy Broughton, Natalie Medlicott
Peripheral BDNF changes after ketamine administration have been proposed as a biomarker for brain BDNF changes. However, published data are conflicting and come from studies in paired animal groups. This study determined the time course of plasma BDNF concentrations following the administration of a single 10 mg/kg dose of ketamine by different routes of administration in rats. Brain BDNF concentrations in prefrontal cortex, hippocampus and cortex were measured in the same animals. Ketamine administration resulted in a rapid and robust increase in plasma BDNF concentrations that were sustained for 240 min...
January 10, 2018: Drug Delivery and Translational Research
https://www.readbyqxmd.com/read/29203848/bdnf-release-and-signaling-are-required-for-the-antidepressant-actions-of-glyx-13
#12
T Kato, M V Fogaça, S Deyama, X-Y Li, K Fukumoto, R S Duman
Conventional antidepressant medications, which act on monoaminergic systems, display significant limitations, including a time lag of weeks to months and low rates of therapeutic efficacy. GLYX-13 is a novel glutamatergic compound that acts as an N-methyl-d-aspartate (NMDA) modulator with glycine-like partial agonist properties; like the NMDA receptor antagonist ketamine GLYX-13 produces rapid antidepressant actions in depressed patients and in preclinical rodent models. However, the mechanisms underlying the antidepressant actions of GLYX-13 have not been characterized...
December 5, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/29162814/trkb-dependent-adult-hippocampal-progenitor-differentiation-mediates-sustained-ketamine-antidepressant-response
#13
Zhenzhong Ma, Tong Zang, Shari G Birnbaum, Zilai Wang, Jane E Johnson, Chun-Li Zhang, Luis F Parada
Adult neurogenesis persists in the rodent dentate gyrus and is stimulated by chronic treatment with conventional antidepressants through BDNF/TrkB signaling. Ketamine in low doses produces both rapid and sustained antidepressant effects in patients. Previous studies have shed light on post-transcriptional synaptic NMDAR mediated mechanisms underlying the acute effect, but how ketamine acts at the cellular level to sustain this anti-depressive function for prolonged periods remains unclear. Here we report that ketamine accelerates differentiation of doublecortin-positive adult hippocampal neural progenitors into functionally mature neurons...
November 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/29161812/acute-amino-acid-d-serine-administration-similar-to-ketamine-produces-antidepressant-like-effects-through-identical-mechanisms
#14
I-Hua Wei, Kuang-Ti Chen, Mang-Hung Tsai, Ching-Hsiang Wu, Hsien-Yuan Lane, Chih-Chia Huang
d-Serine is an amino acid and can work as an agonist at the glycine sites of N-methyl-d-aspartate receptor (NMDAR). Interestingly, both types of glutamatergic modulators, NMDAR enhancers and blockers, can improve depression through common targets, namely alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionaic acid receptors (AMPARs) and mammalian target of rapamycin (mTOR). To elucidate the cellular signaling pathway underlying this counterintuitive observation, we activated NMDARs in rats by using d-serine. Saline, ketamine (NMDAR antagonist), and desipramine (tricyclic antidepressant) were used as controls...
December 13, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29158584/ketamine-enhances-structural-plasticity-in-mouse-mesencephalic-and-human-ipsc-derived-dopaminergic-neurons-via-ampar-driven-bdnf-and-mtor-signaling
#15
L Cavalleri, E Merlo Pich, M J Millan, C Chiamulera, T Kunath, P F Spano, G Collo
Among neurobiological mechanisms underlying antidepressant properties of ketamine, structural remodeling of prefrontal and hippocampal neurons has been proposed as critical. The suggested mechanism involves downstream activation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, which trigger mammalian target of rapamycin (mTOR)-dependent structural plasticity via brain-derived neurotrophic factor (BDNF) and protein neo-synthesis. We evaluated whether ketamine elicits similar molecular events in dopaminergic (DA) neurons, known to be affected in mood disorders, using a novel, translational strategy that involved mouse mesencephalic and human induced pluripotent stem cells-derived DA neurons...
April 2018: Molecular Psychiatry
https://www.readbyqxmd.com/read/29158577/vgf-function-in-depression-and-antidepressant-efficacy
#16
C Jiang, W-J Lin, M Sadahiro, B Labonté, C Menard, M L Pfau, C A Tamminga, G Turecki, E J Nestler, S J Russo, S R Salton
Brain-derived neurotrophic factor (BDNF) is a critical effector of depression-like behaviors and antidepressant responses. Here, we show that VGF (non-acronymic), which is robustly regulated by BDNF/TrkB signaling, is downregulated in hippocampus (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 dorsal hippocampus (dHc) or NAc, led to pro-depressant or antidepressant behaviors, respectively, while dHc- or NAc-AAV-VGF overexpression induced opposite outcomes...
November 21, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/29039254/the-antidepressant-efficacy-of-subanesthetic-dose-ketamine-does-not-correlate-with-baseline-subcortical-volumes-in-a-replication-sample-with-major-depressive-disorder
#17
Mark J Niciu, Nicolas D Iadarola, Dipavo Banerjee, David A Luckenbaugh, Minkyung Park, Marc Lener, Lawrence Park, Dawn F Ionescu, Elizabeth D Ballard, Nancy E Brutsche, Nirmala Akula, Francis J McMahon, Rodrigo Machado-Vieira, Allison C Nugent, Carlos A Zarate
BACKGROUND: This study sought to reproduce, in a larger sample, previous findings of a correlation between smaller raw 3-Tesla (3T) hippocampal volumes and improved antidepressant efficacy of ketamine in individuals with major depressive disorder (MDD). A secondary analysis stratified subjects according to functional BDNF rs6265 (val66met) genotype. METHODS: Unmedicated subjects with treatment-resistant MDD ( n=55) underwent baseline structural 3T MRI. Data processing was conducted with FSL/FIRST and Freesurfer software...
December 2017: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/29020410/the-requirement-of-l-type-voltage-dependent-calcium-channel-l-vdcc-in-the-rapid-acting-antidepressant-like-effects-of-scopolamine-in-mice
#18
Hanjie Yu, Mengmeng Li, Xinbei Shen, Dan Lv, Xin Sun, Jinting Wang, Xinmei Gu, Jingning Hu, Chuang Wang
Background: Previous studies have shown that a low dose of scopolamine produces rapid-acting antidepressant-like actions in rodents. Understanding the mechanisms underlying this effect and the dose-dependent variations of drug responses remains an important task. L-type voltage-dependent calcium channels were found to mediate rapid-acting antidepressant effects of certain medications (e.g., ketamine). Therefore, it is of great interest to determine the involvement of L-type voltage-dependent calcium channels in the action of scopolamine...
February 1, 2018: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28947331/ketamine-and-aminoguanidine-differentially-affect-bdnf-and-mtor-gene-expression-in-the-prefrontal-cortex-of-adult-male-rats
#19
Vitor Silva Pereira, Betina Elfving, Sâmia R L Joca, Gregers Wegener
The rapid and sustained antidepressant properties of ketamine provide evidence of the importance of the glutamatergic system in the neurobiology of depression. The antidepressant-like effects of ketamine are dependent on brain-derived neurotrophic factor (BDNF) and mammalian target of rapamycin (mTOR) in limbic brain areas. The nitrergic system is closely related to the glutamatergic system and generates antidepressant-like effects when blocked. The aim of this study was to investigate whether the behavioural effects induced by the inhibition of nitric oxide (NO) synthesis by aminoguanidine or N-methyl-D-aspartate (NMDA) receptor blockade by ketamine would affect the gene expression of Bdnf and Mtor in the ventromedial prefrontal cortex in rats...
November 15, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28939975/ketamine-induced-glutamatergic-mechanisms-of-sleep-and-wakefulness-insights-for-developing-novel-treatments-for-disturbed-sleep-and-mood
#20
Wallace C Duncan, Elizabeth D Ballard, Carlos A Zarate
Ketamine, a drug with rapid antidepressant effects and well-described effects on slow wave sleep (SWS), is a useful intervention for investigating sleep-wake mechanisms involved in novel therapeutics. The drug rapidly (within minutes to hours) reduces depressive symptoms in individuals with major depressive disorder (MDD) or bipolar disorder (BD), including those with treatment-resistant depression. Ketamine treatment elevates extracellular glutamate in the prefrontal cortex. Glutamate, in turn, plays a critical role as a proximal element in a ketamine-initiated molecular cascade that increases synaptic strength and plasticity, which ultimately results in rapidly improved mood...
September 23, 2017: Handbook of Experimental Pharmacology
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