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Neuropharmacology

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https://www.readbyqxmd.com/read/29331305/tigar-inhibits-ischemia-reperfusion-induced-inflammatory-response-of-astrocytes
#1
Jieyu Chen, Ding-Mei Zhang, Xing Feng, Jian Wang, Yuan-Yuan Qin, Tian Zhang, Qiao Huang, Rui Sheng, Zhong Chen, Mei Li, Zheng-Hong Qin
The inflammatory response of glial cells contributes to neuronal damage or repair after brain ischemia/reperfusion insult. We previously demonstrated a protective role of TP53-induced glycolysis and apoptosis regulator (TIGAR) in ischemic neuronal injury through increasing the flow of pentose phosphate pathway (PPP). The present study investigated the possible role of TIGAR in ischemia/reperfusion-induced inflammatory response of astrocytes. Male ICR mice were subjected to middle cerebral artery occlusion for 2 h followed by 24 h reperfusion and cultured primary astrocytes were subjected to oxygen glucose deprivation for 9 h followed by 24 h reoxygenation (OGD/R)...
January 10, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29329879/mir-134-modulates-chronic-stress-induced-structural-plasticity-and-depression-like-behaviors-via-downregulation-of-limk1-cofilin-signaling-in-rats
#2
Cuiqin Fan, Xiuzhi Zhu, Qiqi Song, Peng Wang, Zhuxi Liu, Shu Yan Yu
Increasing evidence has suggested that depression is a neuropsychiatric condition associated with neuroplasticity within specific brain regions. However, the mechanisms by which neuroplasticity exerts its effects in depression remain largely uncharacterized. In the present study we show that chronic stress effectively induces depression-like behaviors in rats, an effect which was associated with structural changes in dendritic spines and synapse abnormalities within neurons of the ventromedial prefrontal cortex (vmPFC)...
January 9, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29325900/orexin-b-modulates-synaptic-transmission-of-rod-bipolar-cells-in-rat-retina
#3
Gong Zhang, Xiao-Hua Wu, Guo-Zhong Xu, Shi-Jun Weng, Xiong-Li Yang, Yong-Mei Zhong
Orexin-A, -B play a crucial role in arousal and feeding by activating two G-protein-coupled receptors: orexin receptor 1 (OX1R) and orexin receptor 2 (OX2R). Orexins, along with orexin receptors, are expressed in retinal neurons, and they have been shown to differentially modulate excitatory AMPA receptors of amacrine and ganglion cells in the inner retina. In this work we report that orexin-B modulates the activity of rod bipolar cells (RBCs) located in the outer retina of rat. Intravitreal injection of orexin-B increased the amplitude of the scotopic electroretinographic b-wave, a reflection of RBC activity, recorded in vivo...
January 8, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29325899/do-ketone-bodies-mediate-the-anti-seizure-effects-of-the-ketogenic-diet
#4
REVIEW
Timothy A Simeone, Kristina A Simeone, Carl E Stafstrom, Jong M Rho
Although the mechanisms underlying the anti-seizure effects of the high-fat ketogenic diet (KD) remain unclear, a long-standing question has been whether ketone bodies (i.e., beta-hydroxybutyrate [BHB], acetoacetate [ACA] and acetone), either alone or in combination, contribute mechanistically. The traditional belief has been that while ketone bodies reflect enhanced fatty acid oxidation and a general shift toward intermediary metabolism, they are not likely to be the key mediators of the KD's clinical effects, as blood levels of BHB do not correlate consistently with improved seizure control...
January 8, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29317225/anatomical-recovery-of-the-gabaergic-system-after-a-complete-spinal-cord-injury-in-lampreys
#5
D Romaus-Sanjurjo, S M Valle-Maroto, A Barreiro-Iglesias, B Fernández-López, M C Rodicio
Lampreys recover locomotion spontaneously several weeks after a complete spinal cord injury. Dysfunction of the GABAergic system following SCI has been reported in mammalian models. So, it is of great interest to understand how the GABAergic system of lampreys adapts to the post-injury situation and how this relates to spontaneous recovery. The spinal cord of lampreys contains 3 populations of GABAergic neurons and most of the GABAergic innervation of the spinal cord comes from these local cells. GABAB receptors are expressed in the spinal cord of lampreys and they play important roles in the control of locomotion...
January 6, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29309770/a-sub-set-of-psychoactive-effects-may-be-critical-to-the-behavioral-impact-of-ketamine-on-cocaine-use-disorder-results-from-a-randomized-controlled-laboratory-study
#6
REVIEW
E Dakwar, E V Nunes, C L Hart, M C Hu, R W Foltin, F R Levin
Efforts to translate sub-anesthetic ketamine infusions into widespread clinical use have centered around developing medications with comparable neurobiological activity, but with attenuated psychoactive effects so as to minimize the risk of behavioral toxicity and abuse liability. Converging lines of research, however, suggest that some of the psychoactive effects of sub-anesthetic ketamine may have therapeutic potential. Here, we assess whether a subset of these effects - the so-called mystical-type experience - mediates the effect of ketamine on craving and cocaine use in cocaine dependent research volunteers...
January 5, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29309769/sloh-a-carbazole-based-fluorophore-mitigates-neuropathology-and-behavioral-impairment-in-the-triple-transgenic-mouse-model-of-alzheimer-s-disease
#7
Xiaoli Wu, Jayasankar Kosaraju, Wei Zhou, Kin Yip Tam
Alzheimer's disease (AD) is a progressive neurodegenerative dysfunction characterized by memory impairment and brings a heavy burden to old people both in developing and developed countries. Amyloid hypothesis reveals that aggregation and deposition of amyloid plaques are the cause of AD neurodegeneration. SLOH, a carbazole-based fluorophore, is reported to inhibit amyloid beta (Aβ) aggregation in vitro. In the current study, we intended to evaluate the protective effect of SLOH in a triple transgenic AD mouse model (3xTg-AD)...
January 5, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29307544/role-of-mglu7-receptor-in-morphine-rewarding-effects-is-uncovered-by-a-novel-orthosteric-agonist
#8
Zuzana Hajasova, Corinne Canestrelli, Francine Acher, Florence Noble, Nicolas Marie
Opiate dependence is a major health issue and despite the existence of opioid substitution treatment, relapse frequently occurs. Group III metabotropic glutamate (mGlu) receptors has received much attention as a putative target in ethanol and cocaine addiction, but no data on opiate addiction exist. So we investigated the role of group III mGlu receptor in morphine rewarding effects through the expression and the reinstatement of conditioned place preference (CPP) using a newly synthesized mGlu4/mGlu7 receptor orthosteric agonist, LSP2-9166...
January 4, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29307543/neurotensin-speeds-inhibition-of-dopamine-neurons-through-temporal-modulation-of-gabaa-and-gabab-receptor-mediated-synaptic-input
#9
Christopher W Tschumi, Michael J Beckstead
Midbrain dopamine neurons play physiological roles in many processes including reward learning and motivated behavior, and are tonically inhibited by γ-aminobutyric acid (GABA)ergic input from multiple brain regions. Neurotensin (NT) is a neuropeptide which acutely modulates midbrain dopamine neuron excitability through multiple mechanisms, one of which is a decrease of GABA-mediated inhibition. However, the mechanisms through which NT depresses GABA signaling are not known. Here we used whole cell patch-clamp electrophysiology of dopamine neurons in mouse brain slices to show that NT acts both presynaptically to increase GABAA and postsynaptically to decrease GABAB receptor-mediated currents in the substantia nigra...
January 4, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29305122/liraglutide-ameliorates-cognitive-decline-by-promoting-autophagy-via-the-amp-activated-protein-kinase-mammalian-target-of-rapamycin-pathway-in-a-streptozotocin-induced-mouse-model-of-diabetes
#10
Fei-Juan Kong, Jia-Hua Wu, Shui-Ya Sun, Lei-Lei Ma, Jia-Qiang Zhou
Diabetic cognitive dysfunction has gained widespread attention for its deleterious impact on individuals with diabetes. However, few clinical interventions are available to prevent the disorder. The glucagon-like peptide-1 analog liraglutide exerts neuroprotective effects in several models of neurodegenerative diseases. We investigated the effect of liraglutide pretreatment on diabetes-induced cognitive decline and explored the underlying mechanisms in vivo and in vitro. Liraglutide pretreatment prevented diabetes-induced cognitive impairment as assessed by the Morris Water Maze test, and alleviated neuronal injuries and ultrastructural damage to synapses in the hippocampal CA1 region...
January 2, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29305121/allosteric-interactions-between-gabab1-subunits-control-orthosteric-binding-sites-occupancy-within-gabab-oligomers
#11
REVIEW
Gregory D Stewart, Laëtitia Comps-Agrar, Lenea Blanc Nørskov-Lauritsen, Jean-Philippe Pin, Julie Kniazeff
The GABAB receptor was the first G protein-coupled receptor identified as an obligate heterodimer. It is composed of two subunits, GABAB1 containing the agonist binding site and GABAB2 responsible for G protein activation. The GABAB receptor was found to associate into larger complexes through GABAB1-GABAB1 interactions, both in transfected cells and in brain membranes. Here we assessed the possible allosteric interactions between GABAB heterodimers by analyzing the effect of mutations located at the putative interface between the extracellular binding domains...
January 2, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29291424/enhanced-incentive-motivation-in-obesity-prone-rats-is-mediated-by-nac-core-cp-ampars
#12
Rifka C Derman, Carrie R Ferrario
Studies in humans suggest that stronger incentive motivational responses to Pavlovian food cues may drive over-consumption leading to and maintaining obesity, particularly in susceptible individuals. However, whether this enhanced incentive motivation emerges as a consequence of obesity or rather precedes obesity is unknown. Moreover, while human imaging studies have provided important information about differences in striatal responsiveness between susceptible and non-susceptible individuals, the neural mechanisms mediating these behavioral differences are unknown...
December 29, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29288686/increased-amygdala-responses-to-emotional-faces-after-psilocybin-for-treatment-resistant-depression
#13
REVIEW
Leor Roseman, Lysia Demetriou, Matthew B Wall, David J Nutt, Robin L Carhart-Harris
Recent evidence indicates that psilocybin with psychological support may be effective for treating depression. Some studies have found that patients with depression show heightened amygdala responses to fearful faces and there is reliable evidence that treatment with SSRIs attenuates amygdala responses (Ma, 2015). We hypothesised that amygdala responses to emotional faces would be altered post-treatment with psilocybin. In this open-label study, 20 individuals diagnosed with moderate to severe, treatment-resistant depression, underwent two separate dosing sessions with psilocybin...
December 27, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29284138/psychiatry-the-psychedelic-drugs-past-present-future
#14
REVIEW
James J H Rucker, Jonathan Iliff, David J Nutt
The classical psychedelic drugs, including psilocybin, lysergic acid diethylamide and mescaline, were used extensively in psychiatry before they were placed in Schedule I of the UN Convention on Drugs in 1967. Experimentation and clinical trials undertaken prior to legal sanction suggest that they are not helpful for those with established psychotic disorders and should be avoided in those liable to develop them. However, those with so-called 'psychoneurotic' disorders sometimes benefited considerably from their tendency to 'loosen' otherwise fixed, maladaptive patterns of cognition and behaviour, particularly when given in a supportive, therapeutic setting...
December 25, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29277490/gene-environment-interactions-informing-therapeutic-approaches-to-cognitive-and-affective-disorders
#15
REVIEW
Jake Rogers, Thibault Renoir, Anthony J Hannan
Gene-environment interactions drive experience-dependent changes in the brain that alter cognition, emotion and behaviour. Positive engagement with the environment, through novel experience and physical activity, can improve brain function, although the mechanisms mediating such experience-dependent plasticity remain to be fully elucidated. In this article, we discuss the therapeutic value of environmental stimuli, exercise and environmental enrichment (EE), for cognitive and affective disorders, with implications for the understanding and treatment of depression and anxiety disorders...
December 22, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29277489/c-547-a-6-methyluracil-derivative-with-long-lasting-binding-and-rebinding-on-acetylcholinesterase-pharmacokinetic-and-pharmacodynamic-studies
#16
Konstantin Petrov, Irina Zueva, Irina Kovyazina, Igor Sedov, Sofya Lushchekina, Alexandra Kharlamova, Oksana Lenina, Sergei Koshkin, Yurii Shtyrlin, Evgeny Nikolsky, Patrick Masson
C-547, a potent slow-binding inhibitor of acetylcholinesterase (AChE) was intravenously administered to rat (0.05 mg/kg). Pharmacokinetic profiles were determined in blood and different organs: extensor digitorum longus muscle, heart, liver, lungs and kidneys as a function of time. Pharmacokinetics (PK) was studied using non-compartmental and compartmental analyses. A 3-compartment model describes PK in blood. Most of injected C-547 binds to albumin in the bloodstream. The steady-state volume of distribution (3800 ml/kg) is 15 times larger than the distribution volume, indicating a good tissue distribution...
December 22, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29277488/ghrelin-mediated-neuroprotection-a-possible-therapy-for-parkinson-s-disease
#17
REVIEW
Alwena H Morgan, Daniel J Rees, Zane B Andrews, Jeffrey S Davies
Parkinson's disease is a common age-related neurodegenerative disorder affecting 10 million people worldwide, but the mechanisms underlying its pathogenesis are still unclear. The disease is characterised by dopamine nerve cell loss in the mid-brain and intra-cellular accumulation of α-synuclein that results in motor and non-motor dysfunction. In this review, we discuss the neuroprotective effects of the stomach hormone, ghrelin, in models of Parkinson's disease. Recent findings suggest that it may modulate mitochondrial function and autophagic clearance of impaired organelle in response to changes in cellular energy balance...
December 22, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29274752/chronic-paroxetine-treatment-prevents-disruption-of-methamphetamine-sensitive-circadian-oscillator-in-a-transgenic-mouse-model-of-huntington-s-disease
#18
Koliane Ouk, Juliet Aungier, Marc Cuesta, A Jennifer Morton
Circadian abnormalities seen in Huntington's disease (HD) patients are recapitulated in several HD transgenic mouse models. In mice, alongside the master clock located in the suprachiasmatic nucleus (SCN), two other oscillators may influence circadian behaviour. These are the food-entrainable oscillator (FEO) and the methamphetamine-sensitive circadian oscillator (MASCO). SCN- and MASCO- (but not FEO-) driven rhythms are progressively disrupted in the R6/2 mouse model of HD. MASCO-driven rhythms are induced by chronic treatment with low dose of methamphetamine and characterised by an increase in period length to greater than 24 h...
December 21, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29274751/reduced-expression-of-na-ca2-exchangers-is-associated-with-cognitive-deficits-seen-in-alzheimer-s-disease-model-mice
#19
Shigeki Moriguchi, Satomi Kita, Masahiro Fukaya, Makoto Osanai, Ryo Inagaki, Yuzuru Sasaki, Hisanao Izumi, Kyoji Horie, Junji Takeda, Takashi Saito, Hiroyuki Sakagami, Takaomi C Saido, Takahiro Iwamoto, Kohji Fukunaga
Na+/Ca2+ exchangers (NCXs) are expressed primarily in the plasma membrane of most cell types, where they mediate electrogenic exchange of one Ca2+ for three Na+ ions, depending on Ca2+ and Na+ electrochemical gradients across the membrane. Three mammalian NCX isoforms (NCX1, NCX2, and NCX3) are each encoded by a distinct gene. Here, we report that NCX2 and NCX3 protein and mRNA levels are relatively reduced in hippocampal CA1 of APP23 and APP-KI mice. Likewise, NCX2+/- or NCX3+/- mice exhibited impaired hippocampal LTP and memory-related behaviors...
December 21, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29274367/the-effects-of-incretin-hormones-on-cerebral-glucose-metabolism-in-health-and-disease
#20
REVIEW
Malin Nilsson, Albert Gjedde, Birgitte Brock, Michael Gejl, Jørgen Rungby
Incretin hormones, notably glucagon-like peptide-1 (GLP-1), are gluco-regulatory hormones with pleiotropic effects also in the central nervous system. Apart from a local production of GLP-1, systemic administration of the hormone has been shown to influence a number of cerebral pathologies, including neuroinflammation. Given the brains massive dependence on glucose as its major fuel, we here review the mechanistics of cerebral glucose transport and metabolism, focusing on the deleterious effects of both hypo- and hyperglycaemia...
December 20, 2017: Neuropharmacology
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