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Aqeela Zahra, Jinxiang Jiang, Yunan Chen, Cheng Long, Li Yang
Prenatal exposure to citalopram (CTM), an antidepressant drug, has been associated with altered behavior, including autism-like symptoms in both human and rodent offspring. However, the neurological basis underlying these abnormal behaviors is not well understood. Here, we examined behavioral, morphological, and biochemical alterations in the male and female offspring of C57BL/6 mouse mothers that had been exposed to CTM during the last trimester of gestation. We observed abnormal behavior such as anxiety, altered locomotion and disordered social interactions in 2-5 month old offspring with prenatal CTM exposure...
June 15, 2018: Experimental Neurology
Elena Klatt, Thomas Zumbrunn, Oliver Bandschapp, Thierry Girard, Wilhelm Ruppen
Background and aims The development of postoperative chronic pain (POCP) after surgery is a major problem with a considerable socioeconomic impact. It is defined as pain lasting more than the usual healing, often more than 2-6 months. Recent systematic reviews and meta-analyses demonstrate that the N-methyl-D-aspartate-receptor antagonist ketamine given peri- and intraoperatively can reduce immediate postoperative pain, especially if severe postoperative pain is expected and regional anaesthesia techniques are impossible...
December 29, 2017: Scandinavian Journal of Pain
Zhi-Xuan Xia, Zu-Cheng Shen, Shao-Qi Zhang, Ji Wang, Tai-Lei Nie, Qiao Deng, Jian-Guo Chen, Fang Wang, Peng-Fei Wu
AIMS: Palmitoylation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) subunits or their "scaffold" proteins produce opposite effects on AMPAR surface delivery. Considering AMPARs have long been identified as suitable drug targets for central nervous system (CNS) disorders, targeting palmitoylation signaling to regulate AMPAR function emerges as a novel therapeutic strategy. However, until now, much less is known about the effect of palmitoylation-deficient state on AMPAR function...
June 17, 2018: CNS Neuroscience & Therapeutics
Philipp Schätzle, Marta Esteves da Silva, Roderick P Tas, Eugene A Katrukha, Hai Yin Hu, Corette J Wierenga, Lukas C Kapitein, Casper C Hoogenraad
In neurons, microtubules form dense bundles and run along the length of axons and dendrites. Occasionally, dendritic microtubules can grow from the shaft directly into dendritic spines. Microtubules target dendritic spines that are undergoing activity-dependent changes, but the mechanism by which microtubules enter spines has remained poorly understood. Using live-cell imaging, high-resolution microscopy, and local glutamate uncaging, we show that local actin remodeling at the base of a spine promotes microtubule spine targeting...
June 5, 2018: Current Biology: CB
Rita Turnaturi, Lucia Montenegro, Agostino Marrazzo, Rosalba Parenti, Lorella Pasquinucci, Carmela Parenti
Despite the fact that the benzomorphan skeleton has mainly been employed in medicinal chemistry for the development of opioid analgesics, it is a versatile structure. Its stereochemistry, as well as opportune modifications at the phenolic hydroxyl group and at the basic nitrogen, play a pivotal role addressing the benzomorphan-based compounds to a specific target. In this review, we describe the structure activity-relationships (SARs) of benzomorphan-based compounds acting at sigma 1 receptor (σ1R), sigma 2 receptor (σ2R), voltage-dependent sodium channel, N-Methyl-d-Aspartate (NMDA) receptor-channel complex and other targets...
June 7, 2018: European Journal of Medicinal Chemistry
Brigitte Vanle, William Olcott, Jaime Jimenez, Luma Bashmi, Itai Danovitch, Waguih William IsHak
Among patients with Parkinson's disease (PD), depression is prevalent and disabling, impacting both health outcomes and quality of life. There is a critical need for alternative pharmacological methods to treat PD depression, as mainstream antidepressant drugs are largely ineffective in this population. Currently, there are no recommendations for the optimal treatment of PD neuropsychiatric symptoms. Given the dual antidepressant and anti-dyskinetic effects of ketamine and other N-methyl-D-aspartate (NMDA) antagonists for PD, this review aims to examine the current evidence of NMDA antagonists for treating neuropsychiatric symptoms, including memantine, amantadine, ketamine, dizoclopine, and d-cycloserine...
June 15, 2018: Translational Psychiatry
Augusto P I Gargiulo, María P Gargiulo De Aranda, Mercedes M L Gargiulo, Angel J M Gargiulo, Andres Acuña, Gustavo C Baiardi, José V Lafuente, Adriana I Landa De Gargiulo, Manuel A Guevara, Pascual A Gargiulo
BACKGROUND: In previous studies, we have observed that specific N-methyl-d-aspartic acid (NMDA) antagonists and non-NMDA antagonists injected within the nucleus accumbens septi (NAS) induced an anxiolytic-like effect in the plus maze test in rats. In the present study, the effect of intracanalicular blockade of NMDA receptors using dizocilpine in the plus maze was studied in male rats bilaterally cannulated NAS. METHODS: Rats were divided into five groups that received either 1 μL injections of saline or dizocilpine (MK-801, [5R,10S]-[+]-5-methyl-10,11-dihydro-5H-dibenzo [a,d] cyclohepten-5,10-imine) in different doses (0...
June 27, 2018: Journal of Basic and Clinical Physiology and Pharmacology
N A Uvais
No abstract text is available yet for this article.
January 2018: Journal of Pediatric Neurosciences
Inara F Raupp-Barcaro, Maria A Vital, José C Galduróz, Roberto Andreatini
OBJECTIVE: Amantadine blocks N-methyl-D-aspartate (NMDA) receptors and has dopaminergic and noradrenergic action, a neurochemical profile that suggests its potential as an antidepressant drug. We conducted a systematic review of preclinical and clinical studies addressing the effects of amantadine in animal models of depression and in patients with depression. METHODS: PubMed, Science Direct, and Web of Science were searched up to September 1, 2017 to identify clinical and preclinical studies...
June 11, 2018: Revista Brasileira de Psiquiatria
Reem Al Marshad, Razan Al Khatib, Hanine Amer, Munirah Al Shammari, Aysha Al Otaibi, Fahad Al Otaibi, Nadiah Behbehani, Anwaar Al Sayed, Norah Al Hoty, Zuheir Hassan, Amer Kamal
Objective: To investigate the deterioration of the brain functions by diabetes mellitus (DM) and the beneficial effect of caffeine. Materials and Methods: First, the component of N-methyl-D-aspartate receptors (NMDA) of the field excitatory postsynaptic potential (fEPSP) were recorded in streptozotocin (STZ)-induced DM and compared with control animals. Later, 40 mice were divided randomly into five groups (8 mice in each): (1) Normal control (Cont), (2) diabetic group (DM), (3) animals pretreated with i...
May 2018: International Journal of Health Sciences
Rafael Blesa, Kazuhiro Toriyama, Kengo Ueda, Sean Knox, George Grossberg
INTRODUCTION: Alzheimer's disease (AD) is the most common cause of dementia, characterized by a progressive decline in cognition and function. Current treatment options for AD include the cholinesterase inhibitors (ChEIs) donepezil, galantamine, and rivastigmine, as well as the N-methyl-D-aspartate receptor antagonist memantine. Treatment guidelines recommend the use of ChEIs as standard of care first-line therapy. Several randomized clinical studies have demonstrated the benefits of ChEIs on cognition, global function, behavior and activities of daily living...
June 12, 2018: Current Alzheimer Research
Xiaoxuan Yang, Youssef Jounaidi, Jennifer B Dai, Francisco Marte-Oquendo, Elizabeth S Halpin, Lauren E Brown, Richard Trilles, Wenqing Xu, Renee Daigle, Buwei Yu, Scott E Schaus, John A Porco, Stuart A Forman
BACKGROUND: Many general anesthetics were discovered empirically, but primary screens to find new sedative-hypnotics in drug libraries have not used animals, limiting the types of drugs discovered. The authors hypothesized that a sedative-hypnotic screening approach using zebrafish larvae responses to sensory stimuli would perform comparably to standard assays, and efficiently identify new active compounds. METHODS: The authors developed a binary outcome photomotor response assay for zebrafish larvae using a computerized system that tracked individual motions of up to 96 animals simultaneously...
June 12, 2018: Anesthesiology
Michael Popiolek, Brendan Tierney, Stefanus J Steyn, Michael De Vivo
Cognitive decline and psychosis have been hypothesized to be mediated by N-methyl-D-aspartate receptor (NMDAR) hypofunction. Consistent with this hypothesis, chronic treatment with D-alanine, a co-agonist at the glycine site of the NMDAR, lead to an improvement of positive and cognitive symptoms in schizophrenic patients. D-alanine is oxidized by D-amino acid oxidase (DAAO) thus an inhibitor of DAAO would be expected to enhance D-alanine levels and likewise lead to desirable clinical outcomes. Sodium benzoate, on the basis of D-amino acid inhibition, was observed to display beneficial clinical effects in schizophrenic and Alzheimer's patients...
June 12, 2018: ACS Chemical Neuroscience
Mubeen Janmohamed, Wally Knezevic, Merrilee Needham, Sam Salman
Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a well-recognised disorder, first fully characterised in 2007. The long-term sequelae reported thus far include relapses with typical, as well as partial aspects of the well-defined neuropsychiatric syndrome. Rarely, isolated atypical symptoms (diplopia, ataxia and tremor) have been reported as relapse phenomenon. We report a case of a patient with a remote history of likely anti-NMDAR encephalitis with the longest follow-up reported in the literature to date (22 years)...
June 10, 2018: BMJ Case Reports
Alvin Yu, Albert Y Lau
At central nervous system synapses, agonist binding to postsynaptic ionotropic glutamate receptors (iGluRs) results in signaling between neurons. N-Methyl-D-aspartic acid (NMDA) receptors are a unique family of iGluRs that activate in response to the concurrent binding of glutamate and glycine. Here, we investigate the process of agonist binding to the GluN2A (glutamate binding) and GluN1 (glycine binding) NMDA receptor subtypes using long-timescale unbiased molecular dynamics simulations. We find that positively charged residues on the surface of the GluN2A ligand-binding domain (LBD) assist glutamate binding via a "guided-diffusion" mechanism, similar in fashion to glutamate binding to the GluA2 LBD of AMPA receptors...
May 23, 2018: Structure
Julia V Bukanova, Elena I Solntseva, Sergey N Kolbaev, Eva Kudova
The ability of pregnanolone glutamate (PA-Glu), pregnanolone hemisuccinate (PA-hSuc) and pregnanolone hemipimelate (PA-hPim), neuroactive steroids with a negative modulatory effect on excitatory N-methyl-d-aspartate receptors, to influence the functional activity of inhibitory γ-aminobutyric acid and glycine receptors was estimated. The GABA- and glycine-induced chloride currents (IGABA and IGly ) were measured in isolated pyramidal neurons of the rat hippocampus using the patch-clamp technique. Compound PA-Glu was found to potentiate IGABA and to inhibit IGly , while PA-hSuc and PA-hPim inhibited both IGABA and IGly ...
June 7, 2018: Neurochemistry International
Erica Sieg, Michael Brook, Jenny Linnoila, Stephen VanHaerents
We report a 1-year follow-up of a young woman with anti-N-methyl-D-aspartate receptor encephalitis. Management of autoimmune encephalitis remains challenging as objective and clinically relevant biomarkers are sought, which allow for the monitoring of treatment response. While further investigation is required, we believe that this case highlights the importance of following a comprehensive neuropsychological profile as a clinically relevant biomarker to guide therapeutic decision-making. By relying on the neuropsychological assessment of the patient, treatment with more toxic medications was avoided and her antiepileptic drug regimen was simplified...
June 8, 2018: BMJ Case Reports
Marina Gaínza-Lein, Iván Sánchez Fernández, Adriana Ulate-Campos, Tobias Loddenkemper, Adam P Ostendorf
OBJECTIVE: Describe basic science, animal models and clinical data related to timing of treatment in status epilepticus (SE). METHODS: We summarized the results of 15 studies that reported time to treatment in SE, and reviewed basic and clinical literature. RESULTS: SE is a life-threatening and time-sensitive emergency that requires immediate treatment. Current guidelines recommend escalation of anti-seizure medications (ASM) within specified time frames...
June 1, 2018: Seizure: the Journal of the British Epilepsy Association
Semen V Nesterov, Yulia A Skorobogatova, Alisa A Panteleeva, Lyubov L Pavlik, Irina B Mikheeva, Lev S Yaguzhinsky, Yaroslav R Nartsissov
The purpose of this study is to demonstrate the presence of three more receptors in mitochondria. Two N-methyl-d-aspartate receptor (NMDAR) subunits (NR1 and NR2B) are found by protein immunoblot and immunogold labeling in mitochondria fraction isolated from rat heart. These data allow supposing NMDAR presence and functioning in the inner mitochondrial membrane. There are no signs of receptor presence obtained in heart tissue lysate, that indicates the receptor localization exactly in mitochondria. The possible receptor functions discussed are its participation in calcium transport and in excitation-metabolism coupling...
June 5, 2018: Chemico-biological Interactions
Jinfeng Duan, Chengming Lao, Jingkai Chen, Fen Pan, Chenlin Zhang, Weijuan Xu, Weihua Zhou, Jianbo Hu, Desheng Shang, Manli Huang, Yi Xu
Memantine, an N -methyl-d-aspartate receptor antagonist, is a well-established treatment option for moderate-to-severe cognitive impairment related to Alzheimer disease. Recently, growing evidence has indicated memantine might also be effective in treatment of affective disorders. The common drug-induced adverse events of memantine include confusion, dizziness, drowsiness, headache, insomnia, and agitation. Herein, we presented a case of a 73-year-old female patient with vascular neurocognitive disorder, who developed a manic episode after taking memantine...
2018: Neuropsychiatric Disease and Treatment
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