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nmda agonist

Ghulam Hussain, Azhar Rasul, Haseeb Anwar, Nimra Aziz, Aroona Razzaq, Wei Wei, Muhammad Ali, Jiang Li, Xiaomeng Li
Neurodegenerative diseases are conventionally demarcated as disorders with selective loss of neurons. Conventional as well as newer molecules have been tested but they offer just symptomatic advantages along with abundant side effects. The discovery of more compelling molecules that can halt the pathology of these diseases will be considered as a miracle of present time. Several synthetic compounds are available but they may cause several other health issues. Therefore, natural molecules from the plants and other sources are being discovered to replace available medicines...
2018: International Journal of Biological Sciences
Ashley C Nelson, Stephanie B Williams, Stephanie S Pistorius, Hyun J Park, Taylor J Woodward, Andrew J Payne, J Daniel Obray, Samuel I Shin, Jennifer K Mabey, Scott C Steffensen
The neural mechanisms underlying alcohol dependence are not well-understood. GABAergic neurons in the ventral tegmental area (VTA) are a relevant target for ethanol. They are inhibited by ethanol at physiologically-relevant levels in vivo and display marked hyperexcitability during withdrawal. In the present study, we examined the effects of the GABA(A) receptor agonist muscimol on VTA neurons ex vivo following withdrawal from acute and chronic ethanol exposure. We used standard cell-attached mode electrophysiology in the slice preparation to evaluate the effects of muscimol on VTA GABA neuron firing rate following exposure to acute and chronic ethanol in male CD-1 GAD-67 GFP mice...
2018: Frontiers in Neuroscience
Luan Castro Tonelli, Markus Wöhr, Rainer Schwarting, Liana Melo-Thomas
Paradoxical kinesia is a sudden transient ability of akinetic patients to perform motor tasks they are otherwise unable to perform. This phenomenon is known to depend on the patient's emotional state and external stimuli. Paradoxical kinesia can be induced by appetitive 50-kHz ultrasonic vocalizations (USV) in rats displaying catalepsy following systemic haloperidol. We investigated the role of the inferior colliculus (IC) in paradoxical kinesia induced by 50-kHz USV, since the IC modulates haloperidol-induced catalepsy...
March 14, 2018: Neuropharmacology
Stephany M Biello, David R Bonsall, Lynsey A Atkinson, Penny C Molyneux, Mary E Harrington, Gurprit S Lall
Robust physiological circadian rhythms form an integral part of well-being. The aging process has been found to negatively impact systems that drive circadian physiology, typically manifesting as symptoms associated with abnormal/disrupted sleeping patterns. Here, we investigated the age-related decline in light-driven circadian entrainment in male C57BL/6J mice. We compared light-driven resetting of circadian behavioral activity in young (1-2 months) and old (14-18 months) mice and explored alterations in the glutamatergic pathway at the level of the circadian pacemaker, the suprachiasmatic nucleus (SCN)...
February 20, 2018: Neurobiology of Aging
Alejandro Gabriel G Gonzalez Garay, Daniel Molano Franco, Víctor H Nieto Estrada, Arturo J Martí-Carvajal, Ingrid Arevalo-Rodriguez
BACKGROUND: High altitude illness (HAI) is a term used to describe a group of mainly cerebral and pulmonary syndromes that can occur during travel to elevations above 2500 metres (˜ 8200 feet). Acute mountain sickness (AMS), high altitude cerebral oedema (HACE) and high altitude pulmonary oedema (HAPE) are reported as potential medical problems associated with high altitude ascent. In this second review, in a series of three about preventive strategies for HAI, we assessed the effectiveness of five of the less commonly used classes of pharmacological interventions...
March 12, 2018: Cochrane Database of Systematic Reviews
Diana Campos-Beltrán, Åsa Konradsson-Geuken, Jorge E Quintero, Lisa Marshall
D-serine is the major D-amino acid in the mammalian central nervous system. As the dominant co-agonist of the endogenous synaptic NMDA receptor, D-serine plays a role in synaptic plasticity, learning, and memory. Alterations in D-serine are linked to neuropsychiatric disorders including schizophrenia. Thus, it is of increasing interest to monitor the concentration of D-serine in vivo as a relevant player in dynamic neuron-glia network activity. Here we present a procedure for amperometric detection of D-serine with self-referencing ceramic-based microelectrode arrays (MEAs) coated with D-amino acid oxidase from the yeast Rhodotorula gracilis (RgDAAO)...
March 6, 2018: Biosensors
Mohamed R Elnagar, Anne Byriel Walls, Gouda K Helal, Farid M Hamada, Morten Skøtt Thomsen, Anders A Jensen
In the present study, the functional properties of α7 nicotinic acetylcholine receptors (α7 nAChRs) and N-methyl-D-aspartate receptors (NMDARs) endogenously expressed in SH-SY5Y human neuroblastoma cells were characterized in an extracellular-signal regulated kinase (ERK) phosphorylation assay. Both choline and N-methyl-D-aspartate (NMDA) mediated robust concentration-dependent increases in ERK phosphorylation in the SH-SY5Y cells, exhibiting EC50 values in good agreement with those reported for the agonists at recombinant α7 nAChRs and NMDARs, respectively...
March 1, 2018: European Journal of Pharmacology
Marta Portero-Tresserra, Margarita Martí-Nicolovius, Mireia Tarrés-Gatius, Ana Candalija, Gemma Guillazo-Blanch, Anna Vale-Martínez
RATIONALE: Aging is characterized by a decrease in N-methyl-D-aspartate receptors (NMDARs) in the hippocampus, which might be one of the factors involved in the age-dependent cognitive decline. D-Cycloserine (DCS), a partial agonist of the NMDAR glycine recognition site, could improve memory deficits associated to neurodegenerative disorders and cognitive deficits observed in normal aging. OBJECTIVES AND METHODS: The aim of the present study was to explore whether DCS would reverse age-dependent memory deficits and decreases in NMDA receptor subunits (GluN1, GluN2A, and GluN2B) and the presynaptic protein synaptophysin in Wistar rats...
February 28, 2018: Psychopharmacology
Nazanin R Kondori, Praveen Paul, Jacqueline P Robbins, Ke Liu, John C W Hildyard, Dominic J Wells, Jacqueline S de Belleroche
We have investigated a pathogenic mutation in D-amino acid oxidase (DAO), DAOR199W , associated with familial Amyotrophic Lateral Sclerosis (ALS) that impairs D-serine metabolism and causes protein aggregation, autophagy and cell death in motor neuron cell lines. These features are consistent with the pathogenic processes occurring in ALS but most importantly, we have demonstrated that activation of the formation of ubiquitinated protein inclusions, increased autophagosome production and apoptotic cell death caused by the mutation in cell lines are attenuated by 5,7-dichlorokynurenic acid (DCKA), a selective inhibitor of the glycine/D-serine binding site of the NMDA receptor...
2018: Frontiers in Molecular Biosciences
Emiliano Merlo, Amy L Milton, Barry J Everitt
Fully consolidated fear memories can be maintained or inhibited by retrieval-dependent mechanisms depending on the degree of re-exposure to fear cues. Short exposures promote memory maintenance through reconsolidation and long exposures promote inhibition through extinction. Little is known about the neural mechanisms by which increasing cue exposure overrides reconsolidation and instead triggers extinction. Using auditory fear conditioning in male rats, we analysed the role of a molecular mechanism common to reconsolidation and extinction of fear, ERK1/2 activation within the basolateral amygdala (BLA), after intermediate CS exposure events...
February 23, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Samuel A Barnes, Jared W Young, Athina Markou, Nika Adham, István Gyertyán, Béla Kiss
RATIONALE: Attentional processing deficits are a core feature of schizophrenia, likely contributing to the persistent functional and occupational disability observed in patients with schizophrenia. The pathophysiology of schizophrenia is hypothesized to involve dysregulation of NMDA receptor-mediated glutamate transmission, contributing to disruptions in normal dopamine transmission. Preclinical investigations often use NMDA receptor antagonists, such as phencyclidine (PCP), to induce cognitive disruptions relevant to schizophrenia...
February 22, 2018: Psychopharmacology
Ioline D Henter, Rafael Teixeira de Sousa, Carlos A Zarate
Both preclinical and clinical studies have implicated glutamatergic system dysfunction in the pathophysiology of mood disorders such as bipolar depression and major depressive disorder. In particular, rapid reductions in depressive symptoms have been noted in response to subanesthetic doses of the glutamatergic modulator ketamine in subjects with major depressive disorder or bipolar depression. These results have prompted the repurposing or development of other glutamatergic modulators, both as monotherapy or adjunctive to other therapies...
February 20, 2018: Harvard Review of Psychiatry
Xingbo Bian, Xiaofeng Liu, Jinping Liu, Yan Zhao, Haijun Li, Enbo Cai, Pingya Li, Yugang Gao
The antidepressant-like effect of chiisanoside from the leaves of Acanthopanax sessiliflorus was evaluated by using mice models of depression, forced swim test (FST) and tail suspension test (TST). The results showed that treatment with chiisanoside at dose of 5.0 mg/kg significantly decreased immobility time in the FST and TST. Pretreatment with haloperidol (a non-selective D2 receptor antagonist), bicuculline (a competitive GABA antagonist) and N-methyl-D-aspartic acid (NMDA, an agonist at the glutamate site) effectively reversed the antidepressant-like effect of chiisanoside (5...
February 16, 2018: International Immunopharmacology
David J Heal, Jane Gosden, Sharon L Smith
Psychedelics comprise drugs come from various pharmacological classes including 5-HT 2A agonists, indirect 5-HT agonists, e.g. MDMA, NMDA antagonists and κ-opioid receptor agonists. There is resurgence in developing psychedelics to treat psychiatric disorders with high unmet clinical need. Many, but not all, psychedelics are schedule 1 controlled drugs (CDs), i.e. no approved medical use. For existing psychedelics in development, regulatory approval will require a move from schedule 1 to a CD schedule for drugs with medical use, i...
February 7, 2018: Neuropharmacology
Rachel Reed, Thomas Doherty
OBJECTIVE: To outline the major components of the minimum alveolar concentration (MAC) and review the literature regarding pharmacological manipulation of the MAC of halothane, isoflurane, sevoflurane, enflurane, and desflurane in dogs. The pharmacological agents included are alpha-2 agonists, benzodiazepines, propofol, opioids, lidocaine, acepromazine, non-steroidal anti-inflammatory agents (NSAIDs), maropitant, and NMDA antagonists. Part 2 of this review will focus on the effect of opioids, lidocaine, NSAIDs, maropitant, acepromazine, and NMDA antagonists on MAC...
February 1, 2018: Research in Veterinary Science
Martin J Acerbo, Olga F Lazareva
Figure-ground segregation is a fundamental visual ability that allows an organism to separate an object from its background. Our earlier research has shown that nucleus rotundus (Rt), a thalamic nucleus processing visual information in pigeons, together with its inhibitory complex, nucleus subpretectalis/interstitio-pretecto-subpretectalis (SP/IPS), are critically involved in figure-ground discrimination (Acerbo et al., 2012; Scully et al., 2014). Here, we further investigated the role of SP/IPS by conducting bilateral microinjections of GABAergic receptor antagonist and agonists (bicuculline and muscimol, respectively) and non-NMDA glutamate receptor antagonist (CNQX) after the pigeons mastered figure-ground discrimination task...
February 2, 2018: Behavioural Brain Research
Caroline B Ferreira, Sergio L Cravo, Sean D Stocker
Obstructive sleep apnea (OSA) is the most common respiratory disturbance of sleep and is closely associated to cardiovascular diseases. In humans, apnea increases respiratory effort and elevates muscle sympathetic nerve activity (SNA), but the primary stimulus for the SNA activation has not been identified. We recently developed a model of apnea in rodents using acute airway obstruction. In this study, we employed this model to test whether the elevation in SNA was mediated by hypoxia, carotid chemoreceptors, or neurotransmission in the nucleus tractus solitarius (NTS)...
February 2018: Physiological Reports
L Melo-Thomas, A L Gil-Martínez, L Cuenca, C Estrada, A Gonzalez-Cuello, R K Schwarting, M T Herrero
The inferior colliculus (IC) is an important midbrain relay station for the integration of descending and ascending auditory information. Additionally, the IC has been implicated in processing sensorimotor responses. Glutamatergic and GABAergic manipulations in the IC can improve motor deficits as demonstrated by the animal model of haloperidol-induced catalepsy. However, how the IC influences motor function remains unclear. We investigated the effects of either intracollicular deep brain stimulation (DBS) or microinjection of the glutamatergic antagonist MK-801 or the agonist NMDA in C57BL/6J mice chronically treated with saline or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)...
January 20, 2018: Neurotoxicology
Andria Pelentritou, Levin Kuhlmann, John Cormack, Will Woods, Jamie Sleigh, David Liley
Anesthesia arguably provides one of the only systematic ways to study the neural correlates of global consciousness/unconsciousness. However to date most neuroimaging or neurophysiological investigations in humans have been confined to the study of γ-Amino-Butyric-Acid-(GABA)-receptor-agonist-based anesthetics, while the effects of dissociative N-Methyl-D-Aspartate-(NMDA)-receptor-antagonist-based anesthetics ketamine, nitrous oxide (N2O) and xenon (Xe) are largely unknown. This paper describes the methods underlying the simultaneous recording of magnetoencephalography (MEG) and electroencephalography (EEG) from healthy males during inhalation of the gaseous anesthetic agents N2O and Xe...
January 13, 2018: Journal of Visualized Experiments: JoVE
Jamileth More, Barbara Bruna, Pedro Lobos, José Luis Galaz, Paula Figueroa, Silvia Namias, Gina Sanchez, Genaro Barrientos, José Luis Valdes, Andrea C Paula-Lima, Cecilia Hidalgo, Tatiana Adasme
Previous studies indicate that hippocampal synaptic plasticity and spatial memory processes entail calcium release from intracellular stores mediated by ryanodine receptor (RyR) channels. In particular, RyR-mediated Ca2+ release is central for the dendritic spine remodeling induced by Brain-Derived Neurotrophic Factor (BDNF), a neurotrophin that stimulates complex signaling pathways leading to memory-associated protein synthesis and structural plasticity. AIMS: To examine if up-regulation of type-2 RyR (RyR2) channels and the spine remodeling induced by BDNF entail reactive oxygen species (ROS) generation, and to test if RyR2 down-regulation affects BDNF-induced spine remodeling and spatial memory...
January 22, 2018: Antioxidants & Redox Signaling
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