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Georgina Perez-Garcia, Miguel A Gama Sosa, Rita De Gasperi, Anna E Tschiffely, Richard M McCarron, Patrick R Hof, Sam Gandy, Stephen T Ahlers, Gregory A Elder
A striking observation among veterans returning from the recent conflicts in Iraq and Afghanistan has been the co-occurrence of blast-related mild traumatic brain injury (mTBI) and post-traumatic stress disorder (PTSD). PTSD and mTBI might coexist due to additive effects of independent psychological and physical traumas experienced in a war zone. Alternatively blast injury might induce PTSD-related traits or damage brain structures that mediate responses to psychological stressors, increasing the likelihood that PTSD will develop following a subsequent psychological stressor...
September 15, 2018: Neuropharmacology
Weinan Sun, Jonathan M Wong, John A Gray, Brett C Carter
NMDA receptors (NMDARs) are essential components in glutamatergic synaptic signaling. The NMDAR antagonist MK-801 has been a valuable pharmacological tool in evaluating NMDAR function because it binds with high affinity to the NMDAR ion channel pore and is non-competitive with ligand binding. MK-801 has also been used to selectively inhibit NMDAR current in only the cell being recorded by including the drug in the intracellular recording solution. Here, we report that intracellular MK-801 (iMK-801) only partially inhibits synaptic NMDAR currents at +40 mV at both cortical layer 4 to layer 2/3 and hippocampal Schaffer collateral to CA1 synapses...
September 15, 2018: Neuropharmacology
Wagner Ak, Kumar Rg
Most areas of medicine use biomarkers in some capacity to aid in understanding how personal biology informs clinical care. This article draws upon the Rehabilomics Research model as a translational framework for programs of precision rehabilitation and intervention research focused on linking personal biology to treatment response using biopsychosocial constructs that broadly represent function that can be applied to many clinical populations with disability. The summary applies the Rehabilomics research framework to the population with traumatic brain injury (TBI) and emphasizes a broad vision for biomarker inclusion, beyond typical brain-derived biomarkers, to capture and/or reflect important neurological and non-neurological pathology associated with TBI as a chronic condition...
September 14, 2018: Neuropharmacology
Vesna Lazarevic, Yunting Yang, Daniela Ivanova, Anna Fejtova, Per Svenningsson
Riluzole is a potent neuroprotective agent which primarily inhibits excitatory neurotransmission interfering with presynaptic release, uptake and postsynaptic actions of glutamate by mechanisms that are not well understood. Riluzole and related prodrugs with improved blood brain barrier penetrance, are shown to be effective for the treatment of amyotrophic lateral sclerosis, ataxias, epilepsy and mood disorders. Our study was undertaken to decipher molecular and subcellular mechanisms of riluzole's antiglutamatergic effect, particularly focusing on presynaptic active zone structure and function...
September 14, 2018: Neuropharmacology
Iqbal Sayeed, Bushra Wali, David B Guthrie, Manohar T Saindane, Michael G Natchus, Dennis C Liotta, Donald G Stein
Although systemic progesterone (PROG) treatment has been shown to be neuroprotective by many laboratories and in multiple animal models of brain injury including traumatic brain injury (TBI). PROG's poor aqueous solubility limits its potential for use as a therapeutic agent. The question of solubility presents challenges for an acute intervention for neural injury, when getting a neuroprotectant to the brain quickly is crucial. Native PROG (nPROG) is hydrophobic and does not readily dissolve in an aqueous-based medium, so this makes it harder to give under emergency field conditions...
September 14, 2018: Neuropharmacology
Roberto De Luca, Karolina Mazur, Anna Kernder, Tatsiana Suvorava, Georg Kojda, Helmut L Haas, Olga A Sergeeva
Histaminergic (HA) neurons located in the tuberomamillary nucleus (TMN) of the posterior hypothalamus fire exclusively during waking and support many physiological functions. We investigated the role of the endovanilloid N-oleoyldopamine (OLDA) in TMN, where dopamine synthesis and its conjugation with oleic acid likely occur. We show that several known targets of OLDA including TRPV1 and cannabinoid receptors are expressed in HA neurons. In contrast to capsaicin, which failed to increase firing of HA neurons in TRPV1 knockout mice (TRPVI KO), OLDA was still able to induce excitation...
September 13, 2018: Neuropharmacology
Xiang Li, Tianyi Wang, Dongping Zhang, Haiying Li, Haitao Shen, Xin Ding, Gang Chen
Microglia activation and neuroinflammation play important roles in intracerebral hemorrhage (ICH)-induced secondary brain injury (SBI). In this study, we attempted to investigate the potential effects of Andrographolide (Andro) on ICH-induced SBI and the possible mechanisms behind these effects. Andro treatment effectively reduced neuronal cell death and degeneration and alleviated neurobehavioral disorders and brain edema in vivo. In an in vitro study, microglia activation-induced neuronal cell death was ameliorated by Andro treatment...
September 12, 2018: Neuropharmacology
E J M Achterberg, M M H van Swieten, D J Houwing, V Trezza, L J M J Vanderschuren
Social play behaviour is a vigorous form of social interaction abundant during the juvenile and adolescent phases of life in many mammalian species, including rats and humans. Social play is thought to be important for social, emotional and cognitive development. Being a rewarding activity, the expression of social play depends on its pleasurable and motivational properties. Since opioids have been widely implicated in reward processes, in the present study we investigated the role of opioids in the pleasurable and motivational properties of social play behaviour in rats...
September 12, 2018: Neuropharmacology
Deborah Peeters, Jonne Rietdijk, Danny Gerrits, Mark Rijpkema, Sietse F de Boer, Robbert-Jan Verkes, Judith R Homberg
RATIONALE: Only a subset of impulsive aggressive patients benefits from selective serotonin reuptake inhibitor (SSRI) treatment, confirming contradictory results about the association between serotonin (5-hydroxytryptamine, 5-HT) and aggression. This shows the need to define behavioral characteristics within this subgroup to move towards individualized pharmacological treatment of impulsive aggression. METHODS: Here we submitted an outbred strain of Long Evans rats to a crossover design treatment regimen with the SSRI citalopram, to test its anti-aggressive effect...
September 11, 2018: Neuropharmacology
Francesca Zoratto, Marco Sbriccoli, Andrea Martinelli, Jeffrey Glennon, Simone Macrì, Giovanni Laviola
Deficits in empathy, the ability to share an emotion of another individual, constitute a hallmark of several psychopathological conditions, including conduct disorder. The co-occurrence of excess rates of aggression, general violation of societal norms and callous-unemotional traits confers specific risk for adult psychopathy. In the present study, we relied on a recently devised experimental model of conduct disorder in mice to test the potential efficacy of intranasal oxytocin administration. Two subgroups of BALB/cJ male mice exhibiting opposite profiles in emotional contagion (i...
September 10, 2018: Neuropharmacology
Rebeca Alvariño, Eva Alonso, Rodney Lacret, Daniel Oves-Costales, Olga Genilloud, Fernando Reyes, Amparo Alfonso, Luis M Botana
Alzheimer's disease (AD) is a pathology characterized by the abnormal accumulation of amyloid-beta (Aβ) and hyperphosphorylated tau. Oxidative stress and neuroinflammation are also strongly related to this disease. The ability of two new glycosylated angucyclinones, streptocyclinones A and B (1 and 2), isolated from Streptomyces sp to improve AD hallmarks was evaluated. Compounds were able to protect SH-SY5Y neuroblastoma cells from H2 O2 -induced oxidative injury by activating the nuclear factor E2-related factor (Nrf2)...
September 8, 2018: Neuropharmacology
Sofia Gustafsson, Tobias Gustavsson, Sahar Roshanbin, Greta Hultqvist, Margareta Hammarlund-Udenaes, Dag Sehlin, Stina Syvänen
The blood-brain barrier (BBB) is suggested to be compromised in Alzheimer's disease (AD). The concomitant presence of vascular amyloid beta (Aβ) pathology, so called cerebral amyloid angiopathy (CAA), also predisposes impairment of vessel integrity. Additionally, immunotherapy against Aβ may lead to further damage of the BBB. To what extent this affects the BBB passage of molecules is debated. The current study aimed to investigate BBB integrity to large molecules in transgenic mice displaying abundant Aβ pathology and age matched wild type animals, with or without acute anti-Aβ antibody treatment...
September 7, 2018: Neuropharmacology
Santiago Mora, Ana Merchan, Olga Vilchez, Susana Aznar, Anders Bue Klein, Lene Ultved, Leticia Campa, Cristina Suñol, Pilar Flores, Margarita Moreno
Serotonin2A receptors and glutamate signaling have been implicated in the pathophysiology and treatment of compulsive spectrum disorders. Schedule-Induced Polydipsia (SIP), characterized by excessive drinking under intermittent food reinforcement schedules, is a valid model for studying the compulsive phenotype in rats. We explored the expression, function, and neurochemistry of 5-HT2A receptors in the frontal cortex (FC) of rats with individual differences to compulsivity. Rats were selected for high (HD) versus low (LD) drinking on SIP...
September 7, 2018: Neuropharmacology
Andrew J Flores, Mitchell J Bartlett, Brandon K Root, Kate L Parent, Michael L Heien, Frank Porreca, Robin Polt, Scott J Sherman, Torsten Falk
Dopamine (DA)-replacement therapy utilizing l-DOPA is the gold standard symptomatic treatment for Parkinson's disease (PD). A critical complication of this therapy is the development of l-DOPA-induced dyskinesia (LID). The endogenous opioid peptides, including enkephalins and dynorphin, are co-transmitters of dopaminergic, GABAergic, and glutamatergic transmission in the direct and indirect striatal output pathways disrupted in PD, and alterations in expression levels of these peptides and their precursors have been implicated in LID genesis and expression...
September 7, 2018: Neuropharmacology
Marieka V DeVuono, Kelly M Hrelja, Lauren Sabaziotis, Alex Rajna, Erin M Rock, Cheryl L Limebeer, David M Mutch, Linda A Parker
Δ9 -tetrahydracannabinol (THC) is recognized as an effective treatment for nausea and vomiting via its action on the cannabinoid 1 (CB1 ) receptor. Paradoxically, there is evidence that THC can also produce nausea and vomiting. Using the conditioned gaping model of nausea in rats, we evaluated the ability of several doses of THC (0.0, 0.5, 5 and 10 mg/kg, i.p.) to produced conditioned gaping reactions. We then investigated the ability of the CB1 receptor antagonist, rimonabant, to block the establishment of THC-induced conditioned gaping...
September 7, 2018: Neuropharmacology
Kathryn Toffolo, Jennifer Osei, William Kelly, Austin Poulsen, Kaitlynn Donahue, Jiefei Wang, Madison Hunter, Jonathan Bard, Jianxin Wang, David Poulsen
Preclinical and clinical studies can be greatly improved through the inclusion of diagnostic, prognostic, predictive or pharmacodynamics biomarkers. Circulating microRNAs (miRNAs) represent highly stable targets that respond to physiological and pathological changes. MicroRNA biomarkers can be detected by highly sensitive and absolutely quantitative methods currently available in most clinical laboratories. Here we review preclinical and clinical studies that have examined circulating miRNAs as potential diagnostic and prognostic biomarkers...
September 6, 2018: Neuropharmacology
Weihua Cai, Shaogen Wu, Zhiqiang Pan, Jifang Xiao, Fei Li, Jing Cao, Weidong Zang, Yuan-Xiang Tao
Hemorrhages occurring within the thalamus lead to a pain syndrome. Clinical treatment of thalamic pain is ineffective, at least in part, due to the elusive mechanisms that underlie the induction and maintenance of thalamic pain. The present study investigated the possible contribution of a protein-protein interaction between postsynaptic density protein 95 (PSD-95) and neuronal nitric oxide synthase (nNOS) to thalamic pain in mice. Thalamic hemorrhage was induced by microinjection of type IV collagenase into unilateral ventral posterior medial/lateral nuclei of the thalamus...
September 5, 2018: Neuropharmacology
Nicolas B Senese, Max Oginsky, Richard R Neubig, Carrie Ferrario, Emily M Jutkiewicz, John R Traynor
A single base mutation in the Gαi2 protein (G184S) renders this Gα subunit insensitive to the negative modulatory effects of Regulator of G-protein Signaling (RGS) proteins. Mice expressing this RGS insensitive (RGSi) variant of Gαi2 (RGSi Gαi2 ) display a spontaneous antidepressant-like phenotype that is reversible by treatment with the 5-HT1A receptor (5-HT1AR) antagonist WAY100635. Here we test the hypothesis that increased activity of 5-HT1ARs in the hippocampus of RGSi Gαi2 knock-in mice is responsible for the expression of the observed antidepressant-like behavior...
September 4, 2018: Neuropharmacology
Fumiko Sekiguchi, Risa Domoto, Kana Nakashima, Daichi Yamasoba, Hiroki Yamanishi, Maho Tsubota, Hidenori Wake, Masahiro Nishibori, Atsufumi Kawabata
Given our recent evidence for the role of high mobility group box 1 (HMGB1) in chemotherapy-induced peripheral neuropathy (CIPN) in rats, we examined the origin of HMGB1 and the upstream and downstream mechanisms of HMGB1 release involved in paclitaxel-induced neuropathy in mice. Paclitaxel treatment developed mechanical allodynia in mice, as assessed by von Frey test, which was prevented by an anti-HMGB1-neutralizing antibody or thrombomodulin alfa capable of inactivating HMGB1. RAGE or CXCR4 antagonists, ethyl pyruvate or minocycline, known to inhibit HMGB1 release from macrophages, and liposomal clodronate, a macrophage depletor, prevented the paclitaxel-induced allodynia...
September 1, 2018: Neuropharmacology
Daniel G Ehlinger, Kathryn G Commons
Human genetic variation in the gene CACNA1C, which codes for the alpha-1c subunit of Cav1.2 L-type calcium channels (LTCCs), has been broadly associated with enhanced risk for neuropsychiatric disorders including major depression, bipolar and schizophrenia. Little is known about the specific neural circuits through which CACNA1C and Cav1.2 LTCCs impact disease etiology. However, serotonin (5-HT) neurotransmission has been consistently implicated in these neuropsychiatric disorders and Cav1.2 LTCCs may influence 5-HT neuron activity during relevant behavioral states such as stress...
August 31, 2018: Neuropharmacology
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