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Bdnf ketamine

Xinran Li, Cen Guo, Yanan Li, Lina Li, Yuxin Wang, Yiming Zhang, Yue Li, Yu Chen, Wenhan Liu, Li Gao
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...
February 16, 2017: Oncotarget
Joan M Striebel, Emily E Nelson, Raj K Kalapatapu
Methoxetamine (MXE) is a ketamine analogue with a high affinity for the N-methyl-D-aspartate (NMDA) receptor. MXE is a newly emerging designer drug of abuse and is widely available through on-line sources and is not detected by routine urine drug screens. In this report, we describe a United States (US) veteran with posttraumatic stress disorder (PTSD) and heavy polysubstance use, who injected high dose MXE for its calming effect. Given MXE's structural similarities to ketamine and recent work showing that ketamine reduces PTSD symptoms, we hypothesize that MXE alleviated this veteran's PTSD symptoms through action at the NMDA receptor and via influences on brain-derived neurotrophic factor (BDNF)...
2017: Case Reports in Psychiatry
Anjali Janardhanan, Anjana Sadanand, Arambakkam Janardhanam Vanisree
OBJECTIVE: Schizophrenia, a common neurological disorder appearing in the late teens or early adulthood, is characterized by disorganized thinking, behaviour, and perception of emotions. Aberrant N-methyl-D-aspartate (NMDA) receptor-mediated synaptic plasticity is a major pathological event here due to dysfunction of dopamine and glutamate transmission at NMDA receptors. De-regulated brain-derived neurotrophic factor (BDNF), i.e., its signalling through the tropomyosin receptor kinase B (TrkB) receptor, is a major feature of schizophrenia...
2016: Neuropsychobiology
R D Idell, G Florova, A A Komissarov, S Shetty, R B S Girard, S Idell
Current understanding of the neurobiology of depression has grown over the past few years beyond the traditional monoamine theory of depression to include chronic stress, inflammation and disrupted synaptic plasticity. Tissue plasminogen activator (tPA) is a key factor that not only promotes fibrinolysis via the activation of plasminogen, but also contributes to regulation of synaptic plasticity and neurogenesis through plasmin-mediated activation of a probrain derived neurotrophic factor (BDNF) to mature BDNF...
March 2017: Medical Hypotheses
Haibiao Guo, Yufang Cheng, Canmao Wang, Jingang Wu, Zhengqiang Zou, Bo Niu, Hui Yu, Haitao Wang, Jiangping Xu
Thus far, phosphodiesterase-4 (PDE4) inhibitors have not been approved for application in Alzheimer's disease (AD) in a clinical setting due to severe side effects, such as nausea and vomiting. In this study, we investigated the effect of FFPM, a novel PDE4 inhibitor, on learning and memory abilities, as well as the underlying mechanism in the APP/PS1 mouse model of AD. Pharmacokinetic studies have revealed that FFPM efficiently permeates into the brain, and reached peak values in plasma 2 h after orally dosing...
January 6, 2017: Neuropharmacology
Chengwei Song, Chengjun Song, Kui Chen, Xiangdong Zhang
BACKGROUND: In vitro culture of neural stem cell-derived neurons serves as an excellent model to study anesthetic-induced neurotoxicity. In our study, we examined the functional role of long non-coding RNA, IGF2AS, in regulating ketamine-induced neurotoxicity in murine neural stem cells. METHODS: Murine E18.5 brain-derived neural stem cells were cultured in vitro. During neural differentiation stage, ketamine-induced gene expression changes of IGF2 and IGF2AS were recorded by qRT-PCR...
January 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Chao Dong, Ji-Chun Zhang, Wei Yao, Qian Ren, Min Ma, Chun Yang, Shigeyuki Chaki, Kenji Hashimoto
BACKGROUND: Similar to the N-methyl-D-aspartate receptor antagonist ketamine, the metabotropic glutamate 2/3 receptor antagonist, MGS0039, shows antidepressant effects. However, there are no reports comparing these 2 compounds in the social defeat stress model of depression. METHODS: We examined the effects of MGS0039 (1 mg/kg) and ketamine (10 mg/kg) on depression-like behavior in susceptible mice after repeated social defeat stress. Protein levels of brain-derived neurotrophic factor, TrkB, phospho-TrkB, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (GluA1), postsynaptic density protein 95, and dendritic spine density in selected brain regions were measured...
October 27, 2016: International Journal of Neuropsychopharmacology
Vivian B Neis, Luis E B Bettio, Morgana Moretti, Priscila B Rosa, Camille M Ribeiro, Andiara E Freitas, Filipe M Gonçalves, Rodrigo B Leal, Ana Lúcia S Rodrigues
Agmatine is an endogenous neuromodulator that has been shown to have antidepressant-like properties. We have previously demonstrated that it can induce a rapid increase in BDNF levels after acute administration, suggesting that agmatine may be a fast-acting antidepressant. To investigate this hypothesis, the present study evaluated the effects of a single administration of agmatine in mice subjected to chronic unpredictable stress (CUS), a model of depression responsive only to chronic treatment with conventional antidepressants...
November 2016: Pharmacology, Biochemistry, and Behavior
Ashley E Lepack, Eunyoung Bang, Boyoung Lee, Jason M Dwyer, Ronald S Duman
Recent preclinical and clinical studies demonstrate that three functionally different compounds, the NMDA receptor channel blocker ketamine, mGlu2/3 receptor antagonist LY341495, and NMDA receptor glycine site agent GLYX-13 produce rapid and long lasting antidepressant effects. Furthermore, these agents are reported to stimulate ERK and mTORC1 signaling in brain. Here we used rat primary cortical culture neurons to further examine the cellular actions of these agents. The results demonstrate that low concentrations of all three compounds rapidly increase levels of the phosphorylated and activated forms of ERK and a downstream target of mTORC1, p70S6 kinase, in a concentration and time dependent manner...
December 2016: Neuropharmacology
Linda Nguyen, Brandon P Lucke-Wold, Aric F Logsdon, Anna L Scandinaro, Jason D Huber, Rae R Matsumoto
Ketamine has been shown to produce rapid and robust antidepressant effects in depressed individuals; however, its abuse potential and adverse psychotomimetic effects limit its widespread use. Dextromethorphan (DM) may serve as a safer alternative on the basis of pharmacodynamic similarities to ketamine. In this proof-of-concept study, behavioral and biochemical analyses were carried out to evaluate the potential involvement of brain-derived neurotrophic factor (BDNF) in the antidepressant-like effects of DM in mice, with comparisons to ketamine and imipramine...
September 28, 2016: Neuroreport
Bangkun Yang, Ji-Chun Zhang, Mei Han, Wei Yao, Chun Yang, Qian Ren, Min Ma, Qian-Xue Chen, Kenji Hashimoto
RATIONALE: The N-methyl-D-aspartate (NMDA) receptor antagonists, including R-ketamine and rapastinel (formerly GLYX-13), show rapid antidepressant effects in animal models of depression. OBJECTIVE: We compared the rapid and sustained antidepressant effects of R-ketamine and rapastinel in the social defeat stress model. RESULTS: In the tail suspension and forced swimming tests, R-ketamine (10 mg/kg, intraperitoneal (i.p.)) or rapastinel (10 mg/kg, i...
October 2016: Psychopharmacology
Xiaozhu Zheng, Chunshui Lin, Yuhong Li, Jing Ye, Jiali Zhou, Peipei Guo
BACKGROUND: Ketamine is an anesthetic commonly used in both humans and animals. Emerging evidence has demonstrated that ketamine may induce neurotoxicity in neural stem cell-derived neurons. In this work, we investigated whether long noncoding RNA (lncRNA) Brain derived neurotrophic factor antisense (BDNF-AS) was involved in ketamine-induced neurotoxicity in differentiation of mouse embryonic neural stem cells. METHODS: Mouse embryonic neural stem cells were differentiated in vitro, and treated with ketamine...
August 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
E M Meylan, L Breuillaud, T Seredenina, P J Magistretti, O Halfon, R Luthi-Carter, J-R Cardinaux
Recent studies implicate the arginine-decarboxylation product agmatine in mood regulation. Agmatine has antidepressant properties in rodent models of depression, and agmatinase (Agmat), the agmatine-degrading enzyme, is upregulated in the brains of mood disorder patients. We have previously shown that mice lacking CREB-regulated transcription coactivator 1 (CRTC1) associate behavioral and molecular depressive-like endophenotypes, as well as blunted responses to classical antidepressants. Here, the molecular basis of the behavioral phenotype of Crtc1(-/-) mice was further examined using microarray gene expression profiling that revealed an upregulation of Agmat in the cortex of Crtc1(-/-) mice...
2016: Translational Psychiatry
Florian Duclot, Iara Perez-Taboada, Katherine N Wright, Mohamed Kabbaj
Only a portion of the population exposed to trauma will develop persistent emotional alterations characteristic of posttraumatic stress disorder (PTSD), which illustrates the necessity for identifying vulnerability factors and novel pharmacotherapeutic alternatives. Interestingly, clinical evidence suggests that novelty seeking is a good predictor for vulnerability to the development of excessive and persistent fear. Here, we first tested this hypothesis by analyzing contextual and cued fear responses of rats selected for their high (high responders, HR) or low (low responders, LR) exploration of a novel environment, indicator of novelty seeking...
October 2016: Neuropharmacology
Wenda Xue, Wei Wang, Tong Gong, Hailou Zhang, Weiwei Tao, Lihong Xue, Yan Sun, Fushun Wang, Gang Chen
Yueju confers antidepressant effects in a rapid and long-lasting manner, similar to ketamine. CREB (cAMP-response element binding protein) signaling is implicated in depression pathology and antidepressant responses. However, the role of CREB and associated brain derived neurotrophic factor (BDNF) signaling in rapid and long-lasting antidepressant effects remains unclear. Here, we demonstrated that ICR and Kunming strain mice conferred antidepressant responses lasting for 1 and 5 days, respectively, following a single dose of Yueju...
2016: Scientific Reports
Xiaolong Wang, Biwen Peng, Chang Xu, Zhengyan Gao, Yuanfei Cao, Zhao Liu, Tongzu Liu
OBJECTIVES: Long-term ketamine abuse can affect the urinary system, resulting in lower urinary tract symptoms (LUTS), but the pathogenesis of this is still unknown. Previous studies have demonstrated that ketamine can change the expression of the brain-derived neurotrophic factor (BDNF) in the serum of ketamine abuse patients. The aim of the present study is to explore the mechanism of the ketamine-mediated BDNF signaling pathway in the bladder of rats on chronic ketamine treatment. METHODS: Rats were randomly assigned to a control (normal saline) or ketamine (30 mg/kg) group, with five rats in each group...
September 2016: International Urology and Nephrology
Theodore A Henderson
While controversial, ketamine has emerged as an effective treatment for refractory depression. Serial infusions have been performed 3 times per week, but our practical experience has challenged this precept concerning infusion frequency. Depression is associated with neuron loss, reduced synapse numbers, and dearborization of dendrites. Ketamine appears to potently induce mechanisms which reverse these neurodegenerative processes. Ketamine not only blocks the glutamate receptor, it activates eukaroyotic elongation factor 2 (eEF2)...
February 2016: Neural Regeneration Research
Vivian Binder Neis, Morgana Moretti, Luis Eduardo B Bettio, Camille M Ribeiro, Priscila Batista Rosa, Filipe Marques Gonçalves, Mark William Lopes, Rodrigo Bainy Leal, Ana Lúcia S Rodrigues
The activation of AMPA receptors and mTOR signaling has been reported as mechanisms underlying the antidepressant effects of fast-acting agents, specially the NMDA receptor antagonist ketamine. In the present study, oral administration of agmatine (0.1mg/kg), a neuromodulator that has been reported to modulate NMDA receptors, caused a significant reduction in the immobility time of mice submitted to the tail suspension test (TST), an effect prevented by the administration of DNQX (AMPA receptor antagonist, 2...
June 2016: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
Yong-Ku Kim, Kyoung-Sae Na
Treatment-resistant depression (TRD) causes substantial socioeconomic burden. Although a consensus on the definition of TRD has not yet been reached, it is certain that classic monoaminergic antidepressants are ineffective for TRD. One decade ago, many researchers found ketamine, an N-methyl-d-aspartate receptor (NMDAR) antagonist, to be an alternative to classic monoaminergic antidepressants. The major mechanisms of action of ketamine rapidly induce synaptogenesis in the brain-derived neurotrophic factor (BDNF) pathway...
October 3, 2016: Progress in Neuro-psychopharmacology & Biological Psychiatry
Kristina Holubova, Lenka Kleteckova, Martina Skurlova, Jan Ricny, Ales Stuchlik, Karel Vales
OBJECTIVE: The aim of our study was to test whether ketamine produces an antidepressant effect in animal model of olfactory bulbectomy and assess the role of mammalian target of rapamycin (mTOR) pathway in ketamine's antidepressant effect. METHODS: Bulbectomized (OBX) rats and sham controls were assigned to four subgroups according to the treatment they received (ketamine, saline, ketamine + rapamycin, and saline + rapamycin). The animals were subjected to open field (OF), elevated plus maze (EPM), passive avoidance (PA), Morris water maze (MWM), and Carousel maze (CM) tests...
2016: Psychopharmacology
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