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Caitlin A Wotton, Elizabeth F Quon, Ashley C Palmer, Lane K Bekar
Both serotonin (5HT) and stress exert changes in cortical inhibitory tone to shape activity of cortical networks. As astrocytes are also known to affect inhibition through established purinergic pathways, we assessed the role of GABA and purinergic pathways in rapid corticosterone (CORT) and 5HT effects on cortical inhibition. We used a paired-pulse paradigm (P1 & P2) in acutely isolated mouse brain slices to evaluate changes in cortical evoked inhibition. Normally, 5HT decreases amplitude of the first pulse P1, while increasing the amplitude of P2 (increase frequency transmission)...
March 15, 2018: Journal of Neuroendocrinology
Muriel Amar, Rómulo Aráoz, Bogdan I Iorga, Takeshi Yasumoto, Denis Servent, Jordi Molgó
Prorocentrolides are members of the cyclic imine phycotoxins family. Their chemical structure includes a 26-membered carbo-macrocycle and a 28-membered macrocyclic lactone arranged around a hexahydroisoquinoline that incorporates the characteristic cyclic imine group. Six prorocentrolides are already known. However, their mode of action remains undetermined. The aim of the present work was to explore whether prorocentrolide A acts on nicotinic acetylcholine receptors (nAChRs), using competition-binding assays and electrophysiological techniques...
February 28, 2018: Toxins
Blanca Perez-Palomar, Irene Mollinedo-Gajate, Esther Berrocoso, J Javier Meana, Jorge E Ortega
Activation of serotonin 5-HT3 receptor (5HT3R) in the locus coeruleus (LC), the principal somatodendritic noradrenergic area, decreases LC firing activity and noradrenaline (NA) release in prefrontal cortex (PFC). Blockade of 5HT3R in coadministration with selective serotonin reuptake inhibitors (SSRIs) has been proposed as a potential strategy to accelerate the onset of action of SSRIs. Dual-probe microdialysis in rats was used to evaluate the involvement of 5HT3R in the in vivo effect exerted by the SSRI citalopram on NA release...
February 22, 2018: Neuropharmacology
Yueh-Ming Tai, Chih-Yuan Ko, Chen-Cheng Lin, Yu-Yue Wan, Jing-Yi Chung, Yia-Ping Liu
OBJECTIVE: Central 5-HT1A receptor is involved in the modulation of sensorimotor gating function. However, its precise role is not clearly defined in developmentally social deprived (isolation rearing, IR) rats featured with impaired sensorimotor gating ability. We therefore aimed to examine the effects of 5HT1A activation on acoustic startle response (ASR) and prepulse inhibition (PPI) in IR rats in a condition of compromised presynaptic 5-HT functions. METHODS: Social control (SOC) and IR rats received an intracerebraoventricular (ICV) injection of 5-HT depletor, 5,7-DHT...
February 2018: Psychiatry Investigation
Jeffery A Goldstein, Lisa A Bastarache, Joshua C Denny, Dan M Roden, Jill M Pulley, David M Aronoff
New therapeutic approaches are needed for gestational diabetes mellitus (GDM), but must show safety and efficacy in a historically understudied population. We studied associations between electronic medical record (EMR) phenotypes and genetic variants to uncover drugs currently considered safe in pregnancy that could treat or prevent GDM. We identified 129 systemically active drugs considered safe in pregnancy targeting the proteins produced from 196 genes. We tested for associations between GDM and/or type 2 diabetes (DM2) and 306 SNPs in 130 genes represented on the Illumina Infinium Human Exome Bead Chip (DM2 was included due to shared pathophysiological features with GDM)...
February 12, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Angela Corvino, Ferdinando Fiorino, Beatrice Severino, Irene Saccone, Francesco Frecentese, Elisa Perissutti, Paola Di Vaio, Vincenzo Santagada, Giuseppe Caliendo, Elisa Magli
The 5-HT1A receptor is a pharmacologically well characterized serotonin receptor subtype and it has long been investigated because of its involvement in several physio-pathological mechanisms and treatment of neurological diseases like ansia and depression. Serotonin (5-HT) also shows many non-neural functions such as essential hypertension, embryogenesis, follicle maturation and behavior. Moreover it exerts a growth factor function on different types of non-tumoral cells, and it was also found to be related to oncogenes...
February 9, 2018: Current Medicinal Chemistry
Ya Fatou Njie-Mbye, Jenaye Robinson, Leah Mitchell-Bush, Marshalyn Mckoy, Catherine A Opere, Sunny E Ohia, Naj Sharif
PURPOSE: To determine the serotonergic (5HT) receptor subtype mediating the contraction of bovine posterior ciliary arteries (BPCAs) in vitro. METHODS: Longitudinal isometric tension was measured in BPCA strips (4-5 mm) mounted in 25 mL organ baths containing oxygenated Krebs solution at 37°C. Cumulative contractile concentration-response (C-R) curves were generated for various 5-HT agonists to assess their potencies and maximal degrees of contraction. Multiple agonist C-R curves were also constructed in the presence and absence of receptor-selective antagonists to determine antagonist potencies using Schild plots...
January 25, 2018: Journal of Ocular Pharmacology and Therapeutics
Matthew R Bailey, Olivia Goldman, Estefanía P Bello, Muhammad O Chohan, Nuri Jeong, Vanessa Winiger, Eileen Chun, Elke Schipani, Abigail Kalmbach, Joseph F Cheer, Peter D Balsam, Eleanor H Simpson
The functionally selective 5HT-2C receptor ligand SB242084 can increase motivation and have rapid onset anti-depressant like effects. We sought to identify the specific behavioural effects of SB242084 treatment and elucidate the mechanism in female and male mice. Using a quantitative behavioural approach we determined that SB242084 increases the vigor and persistence of goal-directed activity across different types of physical work, particularly when work requirements are demanding. We found this influence of SB242084 on effort, rather than reward to be reflected in striatal dopamine measured during behavior...
January 24, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Vandreza Cardoso Bortolotto, Franciane Cabral Pinheiro, Stífani Machado Araujo, Márcia Rósula Poetini, Bianca Santos Bertolazi, Mariane Trindade de Paula, Luana Barreto Meichtry, Francielli Polet de Almeida, Shanda de Freitas Couto, Cristiano Ricardo Jesse, Marina Prigol
Hypothyroidism is often associated with psychiatric disorders such as depression. In this study, we evaluated the effect of chrysin on depressive-like behavior and monoamine levels in hypothyroid female mice. Hypothyroidism was induced by continuous exposure to 0.1% methimazole (MTZ) in drinking water for 31 days. Exposure to MTZ was associated with low plasma levels of thyroid hormones T3 and T4 compared with the control group. Subsequently, euthyroid and MTZ-induced hypothyroid mice were intragastrically administered vehicle or chrysin (20mg/kg) once a day for 28 consecutive days...
January 17, 2018: European Journal of Pharmacology
Ebba Beller, Laura Reuter, Anne Kluge, Christine Preibisch, Ute Lindauer, Alexei Bogdanov, Friederike Lämmer, Claire Delbridge, Kaspar Matiasek, Benedikt J Schwaiger, Tobias Boeckh-Behrens, Claus Zimmer, Alexandra S Gersing
After reperfusion therapy in stroke patients secondary inflammatory processes may increase cerebral damage. In this pilot study, effects of anti-inflammatory therapy were assessed in a middle cerebral artery occlusion (MCAO) mouse model after reperfusion. 1 hour after MCAO, the artery was reopened and tacrolimus or NaCl were administered intra-arterially. Perfusion-weighted (PWI) and diffusion-weighted images (DWI) were obtained by MRI during MCAO. DWI, T2- and T1-weighted images with and without Bis-5HT-DTPA administration were obtained 24 hours after MCAO...
January 15, 2018: Scientific Reports
Irina V Shelukhina, Maxim N Zhmak, Alexander V Lobanov, Igor A Ivanov, Alexandra I Garifulina, Irina N Kravchenko, Ekaterina A Rasskazova, Margarita A Salmova, Elena A Tukhovskaya, Vladimir A Rykov, Gulsara A Slashcheva, Natalya S Egorova, Inessa S Muzyka, Victor I Tsetlin, Yuri N Utkin
Azemiopsin (Az), a linear peptide from the Azemiops feae viper venom, contains no disulfide bonds, is a high-affinity and selective inhibitor of nicotinic acetylcholine receptor (nAChR) of muscle type and may be considered as potentially applicable nondepolarizing muscle relaxant. In this study, we investigated its preclinical profile in regard to in vitro and in vivo efficacy, acute and chronic toxicity, pharmacokinetics, allergenic capacity, immunotoxicity and mutagenic potency. The peptide effectively inhibited (IC50 ~ 19 nM) calcium response of muscle nAChR evoked by 30 μM (EC100) acetylcholine but was less potent (IC50 ~ 3 μM) at α7 nAChR activated by 10 μM (EC50) acetylcholine and had a low affinity to α4β2 and α3-containing nAChR, as well as to GABAA or 5HT₃ receptors...
January 7, 2018: Toxins
Sally A Abuelezz, Nevien Hendawy, Yosra Magdy
As a part of the serotoninergic dysfunction implicated in neurobiology of depression, evidence has focused on serotonin (5-HT) receptors downstream signaling intermediates including glycogen synthase kinase-3β (GSK-3β), cAMP response element binding protein (CREB) and brain derived neurotrophic factor (BDNF). Our team previously reported that coenzyme Q10 (CoQ10) exerted antidepressant-like effect in rats exposed to chronic unpredictable mid stress (CUMS) via elevating serotonin levels. However, the effect of CoQ10 has not been elucidated in downstream signaling molecules mediating 5HT receptors' effect involved in depressive disorder hitherto...
February 1, 2018: Toxicology and Applied Pharmacology
Kathryn H Driesbaugh, Emanuela Branchetti, Juan B Grau, Samuel J Keeney, Kimberly Glass, Mark A Oyama, Nancy Rioux, Salma Ayoub, Michael S Sacks, John Quackenbush, Robert J Levy, Giovanni Ferrari
AIMS: Mitral valve interstitial cells (MVIC) play an important role in the pathogenesis of degenerative mitral regurgitation (MR) due to mitral valve prolapse (MVP). Numerous clinical studies have observed serotonin (5HT) dysregulation in cardiac valvulopathies; however, the impact of 5HT-mediated signaling on MVIC activation and leaflet remodeling in MVP have been investigated to a limited extent. Here we test the hypothesis that 5HT receptors (5HTRs) signaling contributes to MVP pathophysiology...
December 29, 2017: Journal of Molecular and Cellular Cardiology
Oladiran I Olateju, Adhil Bhagwandin, Amadi O Ihunwo, Paul R Manger
We examined the effect of chronic prenatal alcohol exposure on certain neuronal systems involved with the sleep-wake cycle of C57BL/6J mice exposed to prenatal alcohol once they had reached 56 days post-natal. Pregnant mice were exposed to alcohol, through oral gavage, on gestational days 7-16, with recorded blood alcohol concentration (BAC)s averaging 1.84 mg/ml (chronic alcohol group, CA). Two control groups, an oral gavage sucrose control group (chronic alcohol control group, CAc) and a non-treated control group (NTc), were also examined...
2017: Frontiers in Neuroanatomy
Jegath C Athilingam, Roy Ben-Shalom, Caroline M Keeshen, Vikaas S Sohal, Kevin J Bender
The medial prefrontal cortex plays a key role in higher order cognitive functions like decision making and social cognition. These complex behaviors emerge from the coordinated firing of prefrontal neurons. Fast-spiking interneurons (FSIs) control the timing of excitatory neuron firing via somatic inhibition and generate gamma (30-100 Hz) oscillations. Therefore, factors that regulate how FSIs respond to gamma-frequency input could affect both prefrontal circuit activity and behavior. Here, we show that serotonin (5HT), which is known to regulate gamma power, acts via 5HT2A receptors to suppress an inward-rectifying potassium conductance in FSIs...
December 5, 2017: ELife
Liudmila N Novikova, Mallappa K Kolar, Paul J Kingham, Andreas Ullrich, Sven Oberhoffner, Monika Renardy, Michael Doser, Erhard Müller, Mikael Wiberg, Lev N Novikov
Spinal cord injury (SCI) is often associated with scarring and cavity formation and therefore bridging strategies are essential to provide a physical substrate for axonal regeneration. In this study we investigated the effects of a biodegradable conduit made from trimethylene carbonate and ε-caprolactone (TC) containing poly-p-dioxanone microfilaments (PDO) with longitudinal grooves on regeneration after SCI in adult rats. In vitro studies demonstrated that different cell types including astrocytes, meningeal fibroblasts, Schwann cells and adult sensory dorsal root ganglia neurons can grow on the TC and PDO material...
January 15, 2018: Acta Biomaterialia
Arijit Roy, Melissa M J Farnham, Fatemeh Derakhshan, Paul M Pilowsky, Richard J A Wilson
Apneas constitute an acute existential threat to neonates and adults. In large part, this threat is detected by the carotid bodies, the primary peripheral chemoreceptors, and combatted by arousal and acute cardiorespiratory responses, including increased sympathetic output. Similar responses occur with repeated apneas but they continue beyond the last apnea and can persist for hours (i.e. ventilatory and sympathetic LTF). These long-term effects may be adaptive during acute episodic apnea, but may prolong hypertension causing chronic cardiovascular impairment...
November 21, 2017: Journal of Physiology
Antonella Pollano, Verónica Trujillo, Marta M Suárez
Vulnerability to emotional disorders like depression derives from interactions between early and late environments, including stressful conditions. The serotonin (5HT) system is strongly affected by stress and chronic unpredictable stress can alter the 5HT system. We evaluated the distribution of active serotonergic neurons in the dorsal raphe nucleus (DR) through immunohistochemistry in maternally separated and chronically stressed rats treated with an antidepressant, tianeptine, whose mechanism of action is still under review...
November 20, 2017: Stress: the International Journal on the Biology of Stress
Suellen Laís Vicentino-Vieira, Marcelo Biondaro Góis, Aline Rosa Trevizan, Lainy Leiny de Lima, Elen Paula Leatte, Gessilda de Alcântara Nogueira de Melo, João Luiz Garcia, Eduardo José de Almeida Araújo, Débora de Mello Gonçales Sant'Ana
AIM: To evaluate the mucosal tunic and submucosal plexus of the jejunum of rats infected with different inoculum doses of Toxoplasma gondii. MAIN METHODS: Rats were infected with different inoculum doses (50, 500, 1000 and 5000 oocysts) of the T. gondii for 30days, while a control group (CG) received saline solution. Blood and feces were collected before euthanasia for analysis of blood and fecal leukocytes (LEs). Histological analysis of the mucosa, submucosa, villi, crypts and enterocytes were performed...
December 15, 2017: Life Sciences
Matthew L Lazenka, Megan J Moerke, E Andrew Townsend, Kevin B Freeman, F Ivy Carroll, S Stevens Negus
RATIONALE: Nalfurafine is a G protein signaling-biased kappa opioid receptor (KOR) agonist approved in Japan for second-line treatment of uremic pruritus. Neither nalfurafine nor any other KOR agonist is currently approved anywhere for treatment of pain, but recent evidence suggests that G protein signaling-biased KOR agonists may have promise as candidate analgesics/antipruritics with reduced side effects compared to nonbiased or ß-arrestin-signaling-biased KOR agonists. OBJECTIVES: This study compared nalfurafine effects in rats using assays of pain-stimulated and pain-depressed behavior used previously to evaluate other candidate analgesics...
October 24, 2017: Psychopharmacology
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