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Neuropharmacology

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https://www.readbyqxmd.com/read/28238714/neuroprotective-effects-of-kukoamine-a-on-neurotoxin-induced-parkinson-s-model-through-apoptosis-inhibition-and-autophagy-enhancement
#1
XiaoLong Hu, Qi Song, Xin Li, DanDan Li, Qiao Zhang, WeiHong Meng, QingChun Zhao
Parkinson's disease (PD) is characterized by the loss of dopaminergic neurons in substantia nigra (SN). Our previous study demonstrated Kukoamine A to exhibit strong neuroprotective effects through anti-oxidative stress, anti-inflamation, anti-excitoxicity. In the present study, MPP(+) and MPTP-induced PD models of cell and animal were used to investigate the effects of KuA on PD. Our results demonstrated that KuA ameliorated cell loss and mitochondrial membrane potential (MMP) loss, and inhibited Bax/Bcl-2 ratio and MAPKs family that were induced by MPP(+)...
February 24, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28237807/effects-of-paclitaxel-on-the-development-of-neuropathy-and-affective-behaviors-in-the-mouse
#2
Wisam Toma, S Lauren Kyte, Deniz Bagdas, Yasmin Alkhlaif, Shakir D Alsharari, Aron H Lichtman, Zhi-Jian Chen, Egidio Del Fabbro, John W Bigbee, David A Gewirtz, M Imad Damaj
Paclitaxel, one of the most commonly used cancer chemotherapeutic drugs, effectively extends the progression-free survival of breast, lung, and ovarian cancer patients. However, paclitaxel and other chemotherapy drugs elicit peripheral nerve fiber dysfunction or degeneration that leads to peripheral neuropathy in a large proportion of cancer patients. Patients receiving chemotherapy also often experience changes in mood, including anxiety and depression. These somatic and affective disorders represent major dose-limiting side effects of chemotherapy...
February 22, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28235548/chronic-and-acute-adenosine-a2a-receptor-blockade-prevents-long-term-episodic-memory-disruption-caused-by-acute-cannabinoid-cb1-receptor-activation
#3
Francisco M Mouro, Vânia L Batalha, Diana G Ferreira, Joana E Coelho, Younis Baqi, Christa E Müller, Luísa V Lopes, Joaquim A Ribeiro, Ana M Sebastião
Cannabinoid-mediated memory impairment is a concern in cannabinoid-based therapies. Caffeine exacerbates cannabinoid CB1 receptor (CB1R)-induced memory deficits through an adenosine A1 receptor-mediated mechanism. We now evaluated how chronic or acute blockade of adenosine A2A receptors (A2ARs) affects long-term episodic memory deficits induced by a single injection of a selective CB1R agonist. Long-term episodic memory was assessed by the novel object recognition (NOR) test. Mice received an intraperitoneal (i...
February 21, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28232180/increased-thrombospondin-4-after-nerve-injury-mediates-disruption-of-intracellular-calcium-signaling-in-primary-sensory-neurons
#4
Yuan Guo, Zhiyong Zhang, Hsiang-En Wu, Z David Luo, Quinn H Hogan, Bin Pan
Painful nerve injury disrupts Ca(2+) signaling in primary sensory neurons by elevating plasma membrane Ca(2+)-ATPase (PMCA) function and depressing sarco-endoplasmic reticulum Ca(2+)-ATPase (SERCA) function, which decreases endoplasmic reticulum (ER) Ca(2+) stores and stimulates store-operated Ca(2+) entry (SOCE). The extracellular matrix glycoprotein thrombospondin-4 (TSP4), which is increased after painful nerve injury, decreases Ca(2+) current (ICa) through high-voltage-activated Ca(2+) channels and increases ICa through low-voltage-activated Ca(2+) channels in dorsal root ganglion neurons, which are events similar to the effect of nerve injury...
February 20, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28232061/enduring-attenuation-of-norepinephrine-synaptic-availability-and-augmentation-of-the-pharmacological-and-behavioral-effects-of-desipramine-by-repeated-immobilization-stress
#5
Marco A Gonzáles, Ana Pamela Miranda, Horacio Orrego, Rodolfo Silva, María Inés Forray
Here we provide evidence that repeated immobilization stress (RIS) in rats induces a persistent increase in noradrenergic activity in the anterior aspects of the anterolateral bed nucleus of the stria terminalis (alBNST). This increase in noradrenergic activity results from both enhanced synthesis and reuptake of norepinephrine (NE). It leads to a decrease in the synaptic availability of NE, which elicits an augmented noradrenergic response to the inhibitors of NE reuptake (NRIs), such as desipramine (DMI), an antidepressant...
February 20, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28223210/a-novel-glp-1-gip-dual-receptor-agonist-protects-from-6-ohda-lesion-in-a-rat-model-of-parkinson-s-disease
#6
Jaishree Jalewa, Mohit Kumar Sharma, Simon Gengler, Christian Hölscher
The incretins glucagon-like peptide 1 (GLP-1) and glucose dependent insulinotropic polypeptide (GIP) are growth factors that have shown neuroprotective effects in animal models of Parkinson's and Alzheimer's disease. In addition, the GLP-1 mimetic exendin-4 has shown protective effects in a clinical trial in Parkinson's disease (PD) patients. GLP-1 analogues are currently on the market as treatments for type II diabetes. We previously showed that the novel dual agonist (DA-JC1) was effective in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD...
February 20, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28219717/effects-of-tetrahydrocannabinol-on-glucose-uptake-in-the-rat-brain
#7
I Miederer, K Uebbing, J Röhrich, S Maus, N Bausbacher, K Krauter, V Weyer-Elberich, B Lutz, M Schreckenberger, R Urban
Δ(9)-Tetrahydrocannabinol (THC) is the psychoactive component of the plant Cannabis sativa and acts as a partial agonist at cannabinoid type 1 and type 2 receptors in the brain. The goal of this study was to assess the effect of THC on the cerebral glucose uptake in the rat brain. 21 male Sprague Dawley rats (12-13 w) were examined and received five different doses of THC ranging from 0.01 to 1 mg/kg. For data acquisition a Focus 120 small animal PET scanner was used and 24.1-28.0 MBq of [(18)F]-fluoro-2-deoxy-d-glucose were injected...
February 20, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28232062/selective-ligands-for-na-k-atpase-%C3%AE-isoforms-differentially-and-cooperatively-regulate-excitability-of-pyramidal-neurons-in-distinct-brain-regions
#8
Darpan Chakraborty, Olga V Fedorova, Alexei Y Bagrov, Hanoch Kaphzan
Sodium-potassium ATPase (NaKA) is a plasma membrane enzyme responsible for influencing membrane physiology by direct electrogenic activity. It determines cellular excitability and synaptic neurotransmission, thus affecting learning and memory processes. A principle catalytic α subunit of NaKA has development-specific expression pattern. There are two α isoforms, α1 and α3, in adult brain neurons. Although NaKA is a housekeeping enzyme, the physiological differences between these two α isoforms in different brain regions have not been well explored...
February 19, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28223212/n-butilydenephthalide-exhibits-protection-against-neurotoxicity-through-regulation-of-tryptophan-2-3-dioxygenase-in-spinocerebellar-ataxia-type-3
#9
Karthyayani Rajamani, Jen-Wei Liu, Cheng-Han Wu, I-Tsang Chiang, Deng-Huwei You, Si-Yin Lin, Dean-Kuo Hsieh, Shinn-Zong Lin, Horng-Jyh Harn, Tzyy-Wen Chiou
Spinocerebellar ataxia type 3 or Machado-Joseph disease (SCA3/MJD) is characterized by the repetition of a CAG codon in the ataxin-3 gene (ATXN3), which leads to the formation of an elongated mutant ATXN3 protein that can neither be denatured nor undergo proteolysis in the normal manner. This abnormal proteolysis leads to the accumulation of cleaved fragments, which have been identified as toxic and further they act as a seed for more aggregate formation, thereby increasing toxicity in neuronal cells. To date, there have been few studies or treatment strategies that have focused on controlling toxic fragment formation...
February 18, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28223211/sensitizing-exposure-to-amphetamine-increases-ampa-receptor-phosphorylation-without-increasing-cell-surface-expression-in-the-rat-nucleus-accumbens
#10
Qiang Wang, Dongdong Li, Nancy Bubula, Matthew R Campioni, Daniel S McGehee, Paul Vezina
Exposure to psychostimulants like cocaine or amphetamine leads to long-lasting sensitization of their behavioral and neurochemical effects. Here we characterized changes in AMPA receptor distribution and phosphorylation state in the rat nucleus accumbens (NAcc) weeks after amphetamine exposure to assess their potential contribution to sensitization by this drug. Using protein cross-linking, biochemical, subcellular fractionation, and slice electrophysiological approaches in the NAcc, we found that, unlike cocaine, previous exposure to amphetamine did not increase cell surface levels of either GluA1 or GluA2 AMPA receptor subunits, redistribution of these subunits to the synaptic or perisynaptic cellular membrane domains, protein-protein associations required to support the accumulation and retention of AMPA receptors in the PSD, or the peak amplitude of AMPA receptor mediated mEPSCs recorded in NAcc slices...
February 18, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28219718/a-novel-regulatory-role-of-rgs4-in-stat5b-activation-neurite-outgrowth-and-neuronal-differentiation
#11
Paschalina Pallaki, Eirini-Maria Georganta, Ioannis Serafimidis, Maria-Pagona Papakonstantinou, Vassilis Papanikolaou, Sofia Koutloglou, Elsa Papadimitriou, Adamantia Agalou, Aggeliki Tserga, Alexandra Simeonof, Dimitra Thomaidou, Maria Gaitanou, Zafiroula Georgoussi
The Regulator of G protein Signalling 4 (RGS4) is a multitask protein that interacts with and negatively modulates opioid receptor signalling. Previously, we showed that the δ-opioid receptor (δ-OR) forms a multiprotein signalling complex consisting of Gi/Go proteins and the Signal Transducer and Activator of Transcription 5B (STAT5B) that leads to neuronal differentiation and neurite outgrowth upon δ-ΟR activation. Here, we investigated whether RGS4 could participate in signalling pathways to regulate neurotropic events...
February 17, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28216001/loperamide-inhibits-sodium-channels-to-alleviate-inflammatory-hyperalgesia
#12
Ying Wu, Beiyan Zou, Lingli Liang, Min Li, Yuan-Xiang Tao, Haibo Yu, Xiaoliang Wang, Min Li
Previous studies demonstrated that Loperamide, originally known as an anti-diarrheal drug, is a promising analgesic agent primarily targeting mu-opioid receptors. However some evidences suggested that non-opioid mechanisms may be contributing to its analgesic effect. In the present study, Loperamide was identified as a Nav1.7 blocker in a pilot screen. In HEK293 cells expressing Nav1.7 sodium channels, Loperamide blocked the resting state of Nav1.7 channels (IC50 = 1.86 ± 0.11 μM) dose-dependently and reversibly...
February 16, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28216000/pharmacological-and-molecular-characterization-of-the-positive-allosteric-modulators-of-metabotropic-glutamate-receptor-2
#13
REVIEW
L Lundström, C Bissantz, J Beck, M Dellenbach, T J Woltering, J Wichmann, S Gatti
The metabotropic glutamate receptor 2 (mGlu2) plays an important role in the presynaptic control of glutamate release and several mGlu2 positive allosteric modulators (PAMs) have been under assessment for their potential as antipsychotics. The binding mode of mGlu2 PAMs is better characterized in functional terms while few data are available on the relationship between allosteric and orthosteric binding sites. Pharmacological studies characterizing binding and effects of two different chemical series of mGlu2 PAMs are therefore carried out here using the radiolabeled mGlu2 agonist (3)[H]-LY354740 and mGlu2 PAM (3)[H]-2,2,2-TEMPS...
February 16, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28215999/rat-animal-models-for-screening-medications-to-treat-alcohol-use-disorders
#14
REVIEW
Richard L Bell, Sheketha R Hauser, Tiebing Liang, Youssef Sari, Antoinette Maldonado-Devincci, Zachary A Rodd
The purpose of this review is to present animal research models that can be used to screen and/or repurpose medications for the treatment of alcohol abuse and dependence. The focus will be on rats and in particular selectively bred rats. Brief introductions discuss various aspects of the clinical picture, which provide characteristics of individuals with alcohol use disorders (AUDs) to model in animals. Following this, multiple selectively bred rat lines will be described and evaluated in the context of animal models used to screen medications to treat AUDs...
February 16, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28212984/hiv-1-vpr-disrupts-mitochondria-axonal-transport-and-accelerates-neuronal-aging
#15
Ying Wang, Maryline Santerre, Italo Tempera, Kayla Martin, Ruma Mukerjee, Bassel E Sawaya
Disruption of mitochondria axonal transport, essential for the maintenance of synaptic and neuronal integrity and function, has been identified in neurodegenerative diseases. Whether HIV-1 viral proteins affect mitochondria axonal transport is unknown, albeit HIV-associated neurocognitive disorders occur in around half of the patients living with HIV. Therefore, we sought to examine the effect of HIV-1 viral protein R (Vpr) on mitochondria axonal transport. Using mice primary neuronal cultures, we demonstrated that 4-day Vpr treatment reduced the ratio of moving mitochondria associated with (i) less energy (ATP) supply, (ii) reduction in Miro-1 and (iii) increase of α-synuclein which led to loss of microtubule stability as demonstrated by inconsecutive distribution of acetylated α-tubulin along the axons...
February 14, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28196627/environmental-enrichment-enhances-cognitive-flexibility-in-c57bl-6-mice-on-a-touchscreen-reversal-learning-task
#16
Ariel Zeleznikow-Johnston, Emma L Burrows, Thibault Renoir, Anthony J Hannan
Environmental enrichment (EE) is any positive modification of the 'standard housing' (SH) conditions in which laboratory animals are typically held, usually involving increased opportunity for cognitive stimulation and physical activity. EE has been reported to enhance baseline performance of wild-type animals on traditional cognitive behavioural tasks. Recently, touchscreen operant testing chambers have emerged as a way of performing rodent cognitive assays, providing greater reproducibility, translatability and automatability...
February 11, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28192112/multiple-blood-brain-barrier-transport-mechanisms-limit-bumetanide-accumulation-and-therapeutic-potential-in-the-mammalian-brain
#17
Kerstin Römermann, Maren Fedrowitz, Philip Hampel, Edith Kaczmarek, Kathrin Töllner, Thomas Erker, Douglas H Sweet, Wolfgang Löscher
There is accumulating evidence that bumetanide, which has been used over decades as a potent loop diuretic, also exerts effects on brain disorders, including autism, neonatal seizures, and epilepsy, which are not related to its effects on the kidney but rather mediated by inhibition of the neuronal Na-K-Cl cotransporter isoform NKCC1. However, following systemic administration, brain levels of bumetanide are typically below those needed to inhibit NKCC1, which critically limits its clinical use for treating brain disorders...
February 10, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28192111/effects-of-progesterone-administered-after-mptp-on-dopaminergic-neurons-of-male-mice
#18
Nadhir Litim, Marc Morissette, Thérèse Di Paolo
Progesterone neuroprotection of striatal dopamine (DA) in male mice lesioned with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was previously reported when administered before MPTP or an hour after. A dose of MPTP to induce a partial lesion was used to model early stages or prodromal Parkinson. We hypothesized that brain DA can be restored by progesterone administered early (24 h) or later (5 days) after MPTP. Male mice received 4 injections of MPTP (8 mg/kg) and progesterone (8 mg/kg) once daily for 5 days started 24 h or 5 days after MPTP...
February 10, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28188737/genetic-variation-in-the-behavioral-effects-of-buprenorphine-in-female-mice-derived-from-a-murine-model-of-the-oprm1-a118g-polymorphism
#19
Caroline A Browne, Rebecca L Erickson, Julie A Blendy, Irwin Lucki
Pharmacogenetic studies have identified the non-synonymous single nucleotide polymorphism (A118G) in the human mu opioid receptor (MOR) gene (OPRM1) as a critical genetic variant capable of altering the efficacy of opioid therapeutics. To date few studies have explored the potential impact of the OPRM1 A118G polymorphism on the pharmacological effects of buprenorphine (BPN), a potent MOR partial agonist and kappa opioid receptor antagonist, which is approved by the FDA for the treatment of opioid addiction and chronic pain...
February 7, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28185898/sirt2-inhibition-modulate-glutamate-and-serotonin-systems-in-the-prefrontal-cortex-and-induces-antidepressant-like-action
#20
Mercedes Erburu, Irene Muñoz-Cobo, Teresa Diaz-Perdigon, Paolo Mellini, Takayoshi Suzuki, Elena Puerta, Rosa M Tordera
Growing evidence suggests that changes in histone acetylation in specific sites of the chromatin modulate neuronal plasticity and contribute to antidepressant-like action. Sirtuin 2 (SIRT2) is a class III NAD(+)-dependent histone deacetylase involved in transcriptional repression of genes regulating synaptic plasticity. Importantly, a key role for the glutamate system in prefrontal cortex (PFC) synaptic plasticity changes induced by antidepressants has been suggested. Here, we asked whether SIRT2 could be a pharmacological target for depression therapy...
February 6, 2017: Neuropharmacology
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