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https://www.readbyqxmd.com/read/28342763/serotonin-and-neuroplasticity-links-between-molecular-functional-and-structural-pathophysiology-in-depression
#1
REVIEW
Christoph Kraus, Eero Castrén, Siegfried Kasper, Rupert Lanzenberger
Serotonin modulates neuroplasticity, especially during early life, and dysfunctions in both systems likewise contribute to pathophysiology of depression. Recent findings demonstrate that serotonin reuptake inhibitors trigger reactivation of juvenile-like neuroplasticity. How these findings translate to clinical antidepressant treatment in major depressive disorder remains unclear. With this review, we link preclinical with clinical work on serotonin and neuroplasticity to bring two pathophysiologic models in clinical depression closer together...
March 22, 2017: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/28284918/intracortical-microstimulation-differentially-activates-cortical-layers-based-on-stimulation-depth
#2
Mathias Benjamin Voigt, Peter Hubka, Andrej Kral
BACKGROUND: Intracortical microstimulation is one of the most common techniques to causally interfere with neuronal processing, but neuronal recordings spanning the whole cortical depth during stimulation are exceptionally rare. OBJECTIVE/HYPOTHESIS: Here we combined layer-specific intracortical microstimulation with extracellular recordings on the same shank of a linear multi-electrode array to study the effects of electrical stimulation in different cortical depths on intracortical processing in the auditory cortex in vivo...
February 27, 2017: Brain Stimulation
https://www.readbyqxmd.com/read/28284350/ketamine-upregulates-enos-expression-in-human-astroglial-a172-cells-possible-role-in-its-antidepressive-properties
#3
Yael Yuhas, Shai Ashkenazi, Eva Berent, Abraham Weizman
Ketamine is a potent anti-depressive agent. Nitric oxide plays an essential role in neuronal transmission and cerebral blood flow and has been implicated in the pathophysiology of major depressive disorder as well as cardiovascular functioning. We investigated the effect of ketamine on eNOS expression in human A172 astroglial cells. Ketamine (50-500μM) increased eNOS expression at 4-24h in a concentration-dependent manner. This effect was mediated by NMDA receptor, Akt inhibition and ERK1/2 activation and was synergistically augmented by rapamycin...
April 15, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28282425/administration-of-tranexamic-acid-to-patients-undergoing-surgery-for-adolescent-idiopathic-scoliosis-evokes-pain-and-increases-the-infusion-rate-of-remifentanil-during-the-surgery
#4
Nobuko Ohashi, Masayuki Ohashi, Naoto Endo, Tatsuro Kohno
BACKGROUND: We recently reported that tranexamic acid (TXA) evokes pain in rats by inhibiting γ-aminobutyric acid and glycine receptors on neurons in the spinal dorsal horn. Although TXA is commonly used to reduce perioperative blood loss during various surgeries, its potential to induce intraoperative nociception, thereby increasing the need for more analgesics during surgery, has not been investigated. Therefore, this study aimed to investigate whether TXA evokes pain and increases the need for a higher infusion rate of remifentanil in patients undergoing surgery for adolescent idiopathic scoliosis (AIS)...
2017: PloS One
https://www.readbyqxmd.com/read/28275719/a-negative-allosteric-modulator-for-%C3%AE-5-subunit-containing-gaba-receptors-exerts-a-rapid-and-persistent-antidepressant-like-action-without-the-side-effects-of-the-nmda-receptor-antagonist-ketamine-in-mice
#5
Panos Zanos, Mackenzie E Nelson, Jaclyn N Highland, Samuel R Krimmel, Polymnia Georgiou, Todd D Gould, Scott M Thompson
New antidepressant pharmacotherapies that provide rapid relief of depressive symptoms are needed. The NMDA receptor antagonist ketamine exerts rapid antidepressant actions in depressed patients but also side effects that complicate its clinical utility. Ketamine promotes excitatory synaptic strength, likely by producing high-frequency correlated activity in mood-relevant regions of the forebrain. Negative allosteric modulators of GABA-A receptors containing α5 subunits (α5 GABA-NAMs) should also promote high-frequency correlated electroencephalogram (EEG) activity and should therefore exert rapid antidepressant responses...
January 2017: ENeuro
https://www.readbyqxmd.com/read/28250331/elucidation-of-the-role-of-dorsal-raphe-serotonergic-neurons-in-mood-regulation-using-pharmacological-and-viral-vector-based-approaches
#6
Kazuki Nagayasu
 Growing evidence indicates that serotonergic neurons play a crucial role in brain function and dysfunction, such as in major depressive disorder. However, the complexity of serotonergic projections severely hampers the elucidation of their precise mechanisms. Here we summarize our recent studies on the effects of ketamine and olanzapine, which have been reported to be effective in treatment-resistant depression, on dorsal raphe nucleus serotonergic neurons, using microdialysis, electrophysiology experiments, and slice cultures...
2017: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
https://www.readbyqxmd.com/read/28242871/attenuation-of-ketamine-induced-impairment-in-verbal-learning-and-memory-in-healthy-volunteers-by-the-ampa-receptor-potentiator-pf-04958242
#7
M Ranganathan, N DeMartinis, B Huguenel, F Gaudreault, M M Bednar, C L Shaffer, S Gupta, J Cahill, M A Sherif, J Mancuso, L Zumpano, D C D'Souza
There is a need to develop treatments for cognitive impairment associated with schizophrenia (CIAS). The significant role played by N-methyl-d-aspartate receptors (NMDARs) in both the pathophysiology of schizophrenia and in neuronal plasticity suggests that facilitation of NMDAR function might ameliorate CIAS. One strategy to correct NMDAR hypofunction is to stimulate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) as AMPAR and NMDAR functioning are coupled and interdependent. In rats and nonhuman primates (NHP), AMPAR potentiators reduce spatial working memory deficits caused by the nonselective NMDAR antagonist ketamine...
February 28, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28237716/clostridium-perfringens-epsilon-toxin-induces-permanent-neuronal-degeneration-and-behavioral-changes
#8
Winston E Morris, Jorge Goldstein, Leandro M Redondo, Adriana Cangelosi, Patricia Geoghegan, Marcela Brocco, Fabián C Loidl, Mariano E Fernandez-Miyakawa
Clostridium perfringens epsilon toxin (ETX), the most potent toxin produced by this bacteria, plays a key role in the pathogenesis of enterotoxaemia in ruminants, causing brain edema and encephalomalacia. Studies of animals suffering from ETX intoxication describe severe neurological disorders that are thought to be the result of vasogenic brain edemas and indirect neuronal toxicity, killing oligodendrocytes but not astrocytes, microglia, or neurons in vitro. In this study, by means of intravenous and intracerebroventricular delivery of sub-lethal concentrations of ETX, the histological and ultrastructural changes of the brain were studied in rats and mice...
February 22, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28236848/the-fibrinolytic-system-a-new-target-for-treatment-of-depression-with-psychedelics
#9
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
https://www.readbyqxmd.com/read/28202503/vitamin-d-and-depression-cellular-and-regulatory-mechanisms
#10
REVIEW
Michael J Berridge
Depression is caused by a change in neural activity resulting from an increase in glutamate that drives excitatory neurons and may be responsible for the decline in the activity and number of the GABAergic inhibitory neurons. This imbalance between the excitatory and inhibitory neurons may contribute to the onset of depression. At the cellular level there is an increase in the concentration of intracellular Ca(2+) within the inhibitory neurons that is driven by an increase in entry through the NMDA receptors (NMDARs) and through activation of the phosphoinositide signaling pathway that generates inositol trisphosphate (InsP3) that releases Ca(2+) from the internal stores...
April 2017: Pharmacological Reviews
https://www.readbyqxmd.com/read/28115237/initial-characterization-of-behavior-and-ketamine-response-in-a-mouse-knockout-of-the-post-synaptic-effector-gene-anks1b
#11
Rachel M Enga, Ann C Rice, Pamela Weller, Mark A Subler, Daiyoon Lee, Chelsea P Hall, Jolene J Windle, Patrick M Beardsley, Edwin J van den Oord, Joseph L McClay
The human ANKS1B gene encodes an activity-dependent effector of post-synaptic signaling. It was recently associated with neuropsychiatric phenotypes in genome-wide studies. While the biological function of ANKS1B has been partly elucidated, its role in behavior is poorly understood. Here, we breed and characterize a full knockout (KO) for murine Anks1b. We found that the homozygous KO genotype was partially lethal, showing significant deviation from expected segregation ratios at weaning. Behaviorally, KOs exhibited no difference in baseline acoustic startle response, but showed deficits in prepulse inhibition (PPI)...
February 22, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28087359/the-effect-of-nmda-r-antagonism-on-simultaneously-acquired-local-field-potentials-and-tissue-oxygen-levels-in-the-brains-of-freely-moving-rats
#12
John Kealy, Sean Commins, John P Lowry
Non-competitive NMDA receptor antagonists are known to induce psychosis-like symptoms in rodents. Administration of such compounds cause behavioural effects such as memory impairment and hyperlocomotion. Additionally, drugs such as phencyclidine (PCP), ketamine and MK-801 all cause distinctive increases in striatal local field potential (LFP) in the high frequency oscillation (HFO) band in the power spectrum (140-180 Hz). Amperometric sensors provide a means to measure tissue oxygen (tO2; a BOLD-like signal) in the brains of freely-moving rats while simultaneously acquiring LFP using the same electrode...
January 11, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28079589/in-vogue-ketamine-for-neuroprotection-in-acute-neurologic-injury
#13
Josh D Bell
Neurologic deterioration following acute injury to the central nervous system may be amenable to pharmacologic intervention, although, to date, no such therapy exists. Ketamine is an anesthetic and analgesic emerging as a novel therapy for a number of clinical entities in recent years, including refractory pain, depression, and drug-induced hyperalgesia due to newly discovered mechanisms of action and new application of its known pharmacodynamics. In this focused review, the evidence for ketamine as a neuroprotective agent in stroke, neurotrauma, subarachnoid hemorrhage, and status epilepticus is highlighted, with a focus on its applications for excitotoxicity, neuroinflammation, and neuronal hyperexcitability...
April 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28063836/inhibiting-effects-of-rhynchophylline-on-methamphetamine-dependent-zebrafish-are-related-with-the-expression-of-tyrosine-hydroxylase-th
#14
Chen Zhu, Wei Liu, Chaohua Luo, Yi Liu, Chan Li, Miao Fang, Yingbo Lin, Jinying Ou, Minting Chen, Daoqi Zhu, Ken Kin-Lam Yung, Zhixian Mo
In this study, to study the effect of rhynchophylline on TH in midbrain of methamphetamine-induced conditioned place preference (CPP) adult zebrafish, place preference adult zebrafish models were established by methamphetamine (40μg/g) and the expression of TH was observed by immunohistochemistry technique and Western blot. Ketamine (150μg/g), high dose of rhynchophylline (100μg/g) group can significantly reduce the place preference; immunohistochemistry results showed that the number of TH-positive neurons in midbrain was increased in the methamphetamine model group, whereas less TH-positive neurons were found in the ketamine group and high dosage rhynchophylline group...
March 2017: Fitoterapia
https://www.readbyqxmd.com/read/28062203/semi-mechanistic-computer-simulation-of-psychotic-symptoms-in-schizophrenia-with-a-model-of-a-humanized-cortico-striatal-thalamocortical-loop
#15
Athan Spiros, Patrick Roberts, Hugo Geerts
Despite new insights into the pathophysiology of schizophrenia and clinical trials with highly selective drugs, no new therapeutic breakthroughs have been identified. We present a semi-mechanistic Quantitative Systems Pharmacology (QSP) computer model of a biophysically realistic cortical-striatal-thalamo-cortical loop. The model incorporates the direct, indirect and hyperdirect pathway of the basal ganglia and CNS drug targets that modulate neuronal firing, based on preclinical data about their localization and coupling to voltage-gated ion channels...
February 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28043916/ketamine-accelerates-fear-extinction-via-mtorc1-signaling
#16
Matthew J Girgenti, Sriparna Ghosal, Dora LoPresto, Jane R Taylor, Ronald S Duman
Impaired fear extinction contributes to the persistence of post-traumatic stress disorder (PTSD), and can be utilized for the study of novel therapeutic agents. Glutamate plays an important role in the formation of traumatic memories, and in the pathophysiology and treatment of PTSD, highlighting several possible drug targets. Recent clinical studies demonstrate that infusion of ketamine, a glutamate NMDA receptor antagonist, rapidly and significantly reduces symptom severity in PTSD patients. In the present study, we examine the mechanisms underlying the actions of ketamine in a rodent model of fear conditioning, extinction, and renewal...
December 30, 2016: Neurobiology of Disease
https://www.readbyqxmd.com/read/27984263/ketamine-increases-the-function-of-%C3%AE-aminobutyric-acid-type-a-receptors-in-hippocampal-and-cortical-neurons
#17
Dian-Shi Wang, Antonello Penna, Beverley A Orser
BACKGROUND: The "dissociative " general anesthetic ketamine is a well-known N-methyl-D-aspartate receptor antagonist. However, whether ketamine, at clinically relevant concentrations, increases the activity of inhibitory γ-aminobutyric acid (GABA) receptor type A (GABAA) receptors in different brain regions remains controversial. Here, the authors studied the effects of ketamine on synaptic and extrasynaptic GABAA receptors in hippocampal neurons. Ketamine modulation of extrasynaptic GABAA receptors in cortical neurons was also examined...
April 2017: Anesthesiology
https://www.readbyqxmd.com/read/27982047/a-clickable-analogue-of-ketamine-retains-nmda-receptor-activity-psychoactivity-and-accumulates-in-neurons
#18
Christine Emnett, Hairong Li, Xiaoping Jiang, Ann Benz, Joseph Boggiano, Sara Conyers, David F Wozniak, Charles F Zorumski, David E Reichert, Steven Mennerick
Ketamine is a psychotomimetic and antidepressant drug. Although antagonism of cell-surface NMDA receptors (NMDARs) may trigger ketamine's psychoactive effects, ketamine or its major metabolite norketamine could act intracellularly to produce some behavioral effects. To explore the viability of this latter hypothesis, we examined intracellular accumulation of novel visualizable analogues of ketamine/norketamine. We introduced an alkyne "click" handle into norketamine (alkyne-norketamine, A-NK) at the key nitrogen atom...
December 16, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27981535/remote-ischemic-preconditioning-provides-neuroprotection-impact-on-ketamine-induced-neuroapoptosis-in-the-developing-rat-brain
#19
W Ma, Y-Y Cao, S Qu, S-S Ma, J-Z Wang, L-Q Deng, W-J Yuan, J-H Meng
OBJECTIVE: Previous studies have demonstrated that the commonly used anesthetic ketamine can acutely increase apoptosis and have long-lasting detrimental effects on cognitive function as the animal matures. Remote ischemic preconditioning (RIPC) has been confirmed to have a cerebral protective role in animal models of brain damage. The aim of this study was to investigate whether RIPC can protect the developing brain from anesthetic-induced neurotoxicity. MATERIALS AND METHODS: To investigate the protective properties of RIPC, 60 new-born Sprague-Dawley (SD) rats were randomly allocated into four groups: ketamine (20 mg/kg was diluted in saline, six times at an interval of 2 hours); RIPC (left hind row ischemia 5 min, reperfusion 5 min, a total of four cycles); ketamine + RIPC: RIPC was induced at postnatal day 5 and rats underwent the same treatment with the ketamine group after 48 hours; and saline (group vehicle)...
December 2016: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/27973590/investigating-power-density-and-the-degree-of-nonlinearity-in-intrinsic-components-of-anesthesia-eeg-by-the-hilbert-huang-transform-an-example-using-ketamine-and-alfentanil
#20
Feng-Fang Tsai, Shou-Zen Fan, Yi-Shiuan Lin, Norden E Huang, Jia-Rong Yeh
Empirical mode decomposition (EMD) is an adaptive filter bank for processing nonlinear and non-stationary signals, such as electroencephalographic (EEG) signals. EMD works well to decompose a time series into a set of intrinsic mode functions with specific frequency bands. An IMF therefore represents an intrinsic component on its correspondingly intrinsic frequency band. The word of 'intrinsic' means the frequency is totally adaptive to the nature of a signal. In this study, power density and nonlinearity are two critical parameters for characterizing the amplitude and frequency modulations in IMFs...
2016: PloS One
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