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https://www.readbyqxmd.com/read/28344757/leveraging-blood-serotonin-as-an-endophenotype-to-identify-de-novo-and-rare-variants-involved-in-autism
#1
Rui Chen, Lea K Davis, Stephen Guter, Qiang Wei, Suma Jacob, Melissa H Potter, Nancy J Cox, Edwin H Cook, James S Sutcliffe, Bingshan Li
BACKGROUND: Autism spectrum disorder (ASD) is one of the most highly heritable neuropsychiatric disorders, but underlying molecular mechanisms are still unresolved due to extreme locus heterogeneity. Leveraging meaningful endophenotypes or biomarkers may be an effective strategy to reduce heterogeneity to identify novel ASD genes. Numerous lines of evidence suggest a link between hyperserotonemia, i.e., elevated serotonin (5-hydroxytryptamine or 5-HT) in whole blood, and ASD. However, the genetic determinants of blood 5-HT level and their relationship to ASD are largely unknown...
2017: Molecular Autism
https://www.readbyqxmd.com/read/28295852/improved-capacity-to-evaluate-changes-in-intestinal-mucosal-surface-area-using-mathematical-modeling
#2
Chasen J Greig, Robert A Cowles
Quantification of intestinal mucosal growth typically relies on morphometric parameters, commonly villus height, as a surrogate for presumed changes in mucosal surface area (MSA). We hypothesized that using mathematical modeling based on multiple unique measurements would improve discrimination of the effects of interventions on MSA compared to standard measures. To determine the ability of mathematical modeling to resolve differences in MSA, a mouse model with enhanced serotonin (5HT) signaling known to stimulate mucosal growth was used...
March 13, 2017: Microscopy Research and Technique
https://www.readbyqxmd.com/read/28292464/intracellular-acidification-increases-adenosine-transport-in-human-umbilical-vein-endothelial-cells
#3
Natalia Celis, Joaquín Araos, Carlos Sanhueza, Fernando Toledo, Ana R Beltrán, Fabián Pardo, Andrea Leiva, Marco A Ramírez, Luis Sobrevia
INTRODUCTION: Adenosine is taken up via human equilibrative nucleoside transporters 1 (hENT1) and 2 (hENT2) at a physiological extracellular pH (pHo ∼7.4) in human umbilical vein endothelial cells (HUVECs). Acidic pHo increases the uptake of adenosine and 5-hydroxytryptamine (5HT) via hENT4 in this cell type. However, modulation of hENT1 and hENT2 transport activity by the pHi is unknown. We investigated whether hENT1 and hENT2-adenosine transport was regulated by acidic pHi. METHODS: HUVECs loaded with a pH sensitive probe were subjected to 0...
March 2017: Placenta
https://www.readbyqxmd.com/read/28289278/cafeteria-diet-and-probiotic-therapy-cross-talk-among-memory-neuroplasticity-serotonin-receptors-and-gut-microbiota-in-the-rat
#4
J E Beilharz, N O Kaakoush, J Maniam, M J Morris
The western diet is known to have detrimental effects on cognition and the gut microbiota, but few studies have investigated how these may be related. Here, we examined whether a probiotic could prevent diet-induced memory deficits. Rats were pre-exposed to vehicle, low or high doses of VSL#3 for 2 weeks before half were switched from chow to a cafeteria diet (Caf) for 25 days; VSL#3 treatment continued until death. High-dose VSL#3 prevented the diet-induced memory deficits on the hippocampal-dependent place task, but the probiotic caused deficits on the perirhinal-dependent object task, irrespective of diet or dose...
March 14, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28273853/changes-in-brain-monoamines-underlie-behavioural-disruptions-after-zebrafish-diet-exposure-to-polycyclic-aromatic-hydrocarbons-environmental-mixtures
#5
Caroline Vignet, Verena M Trenkel, Annick Vouillarmet, Giampiero Bricca, Marie-Laure Bégout, Xavier Cousin
Zebrafish were exposed through diet to two environmentally relevant polycyclic aromatic hydrocarbons (PAHs) mixtures of contrasted compositions, one of pyrolytic (PY) origin and one from light crude oil (LO). Monoamine concentrations were quantified in the brains of the fish after six month of exposure. A significant decrease in noradrenaline (NA) was observed in fish exposed to both mixtures, while a decrease in serotonin (5HT) and dopamine (DA) was observed only in LO-exposed fish. A decrease in metabolites of 5HT and DA was observed in fish exposed to both mixtures...
March 4, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28247311/elevated-serotonin-interacts-with-angiotensin-ii-to-result-in-altered-valve-interstitial-cell-contractility-and-remodeling
#6
Jessica Perez, Nancy Diaz, Ishita Tandon, Rachel Plate, Christopher Martindale, Kartik Balachandran
While the valvulopathic effects of serotonin (5HT) and angiotensin-II (Ang-II) individually are known, it was not clear how 5HT and Ang-II might interact, specifically in the context of the mechanobiological responses due to altered valve mechanics potentiated by these molecules. In this context, the hypothesis of this study was that increased serotonin levels would result in accelerated progression toward disease in the presence of angiotensin-II-induced hypertension. C57/BL6 J mice were divided into four groups and subcutaneously implanted with osmotic pumps containing: PBS (control), 5HT (2...
February 28, 2017: Cardiovascular Engineering and Technology
https://www.readbyqxmd.com/read/28177659/effects-of-ferulic-acid-on-oxidative-stress-heat-shock-protein-70-connexin-43-and-monoamines-in-hippocampus-of-pentylenetetrazole-kindled-rats
#7
Abdelaziz M Hussein, Khalid M Abbas, Osama A Abulseoud, Elhussainy Mohamed Abouelez Elhussainy
The present study investigated the effects of ferulic acid on pentylenetetrazole (PTZ)-induced seizures, oxidative stress markers (malondialdhyde (MDA), catalase (CAT) and reduced glutathione (GSH)), connexin (Cx) 43, heat shock protein (Hsp) 70 and monoamines (serotonin (5HT) and norepinephrine (NE) levels in a rat model of PTZ-induced kindling. Sixty Sprague Dawley rats were divided into 5 equal groups, a) normal group, b) FA group: normal rats received FA at a dose of 40 mg/kg daily, c) PTZ group: rats received PTZ at a dose of 50 mg/kg i...
February 3, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28129327/prolonged-activation-of-the-htr2b-serotonin-receptor-impairs-glucose-stimulated-insulin-secretion-and-mitochondrial-function-in-min6-cells
#8
Luis Rodrigo Cataldo, María L Mizgier, Roberto Bravo Sagua, Fabián Jaña, César Cárdenas, Paola Llanos, Dolores Busso, Pablo Olmos, José E Galgani, José L Santos, Víctor A Cortés
AIMS: Pancreatic β-cells synthesize and release serotonin (5 hydroxytryptamine, 5HT); however, the role of 5HT receptors on glucose stimulated insulin secretion (GSIS) and the mechanisms mediating this function is not fully understood. The aims of this study were to determine the expression profile of 5HT receptors in murine MIN6 β-cells and to examine the effects of pharmacological activation of 5HT receptor Htr2b on GSIS and mitochondrial function. MATERIALS AND METHODS: mRNA levels of 5HT receptors in MIN6 cells were quantified by RT qPCR...
2017: PloS One
https://www.readbyqxmd.com/read/28095756/low-dose-acute-vanillin-is-beneficial-against-harmaline-induced-tremors-in-rats
#9
Al Asmari Abdulrahman, Kunnathodi Faisal, Ali Al Amri Meshref, Mohammed Arshaduddin
OBJECTIVE: To study the effect of pretreatment with low doses of vanillin, a flavoring agent used as a food additive, on harmaline-induced tremor in rats. METHODS: Sprague Dawley rats (110 ± 5 g) were divided into groups of six animals each. Vanillin (6.25 mg, 12.5 mg, and 25 mg/kg) was administered by gavage to different groups of rats, 30 minutes before the induction of tremor. Harmaline (10 mg/kg, i.p.) was used for the induction of tremor. The latency of onset, duration, tremor intensity, tremor index, and spontaneous locomotor activity were recorded...
March 2017: Neurological Research
https://www.readbyqxmd.com/read/28090679/effect-of-prucalopride-on-intestinal-gas-tolerance-in-patients-with-functional-bowel-disorders-and-constipation
#10
Carolina Malagelada, Adoración Nieto, Sara Mendez, Anna Accarino, Javier Santos, Juan-R Malagelada, Fernando Azpiroz
BACKGROUND: Patients with functional bowel disorders develop gas retention and symptoms in response to intestinal gas loads that are well tolerated by healthy subjects. Stimulation of 5HT-4 receptors in the gut has both prokinetic and antinociceptive effects. AIM: To determine the effect of prucalopride, a highly selective 5HT-4 agonist, on gas transit and tolerance in women with functional bowel disorders complaining of constipation. METHODS: Twenty-four women with functional bowel disorders complaining of constipation were included in the study...
January 15, 2017: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28067625/pituitary-adenylate-cyclase-activating-polypeptide-pacap-has-a-neuroprotective-function-in-dopamine-based-neurodegeneration-in-rat-and-snail-parkinsonian-models
#11
Gabor Maasz, Zita Zrinyi, Dora Reglodi, Dora Petrovics, Adam Rivnyak, Tibor Kiss, Adel Jungling, Andrea Tamas, Zsolt Pirger
Pituitary adenylate cyclase-activating polypeptide (PACAP) rescues dopaminergic neurons from neurodegeneration and improves motor changes induced by 6-hydroxy-dopamine (6-OHDA) in rat parkinsonian models. Recently, we investigated the molecular background of the neuroprotective effect of PACAP in dopamine (DA)-based neurodegeneration using rotenone-induced snail and 6-OHDA-induced rat models of Parkinson's disease. Behavioural activity, monoamine (DA and serotonin), metabolic enzyme (S-COMT, MB-COMT and MAO-B) and PARK7 protein concentrations were measured before and after PACAP treatment in both models...
February 1, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28042198/age-worksite-location-neuromodulators-and-task-performance-in-the-ant-pheidole-dentata
#12
Ysabel Milton Giraldo, Adina Rusakov, Alexandria Diloreto, Adrianna Kordek, James F A Traniello
Social insect workers modify task performance according to age-related schedules of behavioral development, and/or changing colony labor requirements based on flexible responses that may be independent of age. Using known-age minor workers of the ant Pheidole dentata throughout 68% of their 140-day laboratory lifespan, we asked whether workers found inside or outside the nest differed in task performance and if behaviors were correlated with and/or causally linked to changes in brain serotonin (5HT) and dopamine (DA)...
September 2016: Behavioral Ecology and Sociobiology
https://www.readbyqxmd.com/read/28033684/cellular-reactions-and-compensatory-tissue-re-organization-during-spontaneous-recovery-after-spinal-cord-injury-in-neonatal-mice
#13
Rishab S Chawla, Mark Züchner, Maria Mastrangelopoulou, François M Lambert, Joel C Glover, Jean-Luc Boulland
Following incomplete spinal cord injuries, neonatal mammals display a remarkable degree of behavioral recovery. Previously, we have demonstrated in neonatal mice a wholesale re-establishment and reorganization of synaptic connections from some descending axon tracts (Boulland et al., 2013). To assess the potential cellular mechanisms contributing to this recovery, we have here characterized a variety of cellular sequelae following thoracic compression injuries, focusing particularly on cell loss and proliferation, inflammation and reactive gliosis, and the dynamics of specific types of synaptic terminals...
December 29, 2016: Developmental Neurobiology
https://www.readbyqxmd.com/read/28025094/serotonergic-mechanisms-of-trigeminal-meningeal-nociception-implications-for-migraine-pain
#14
Erkan Kilinc, Cindy Guerrero-Toro, Andrey Zakharov, Carmela Vitale, Max Gubert-Olive, Ksenia Koroleva, Arina Timonina, Liliana L Luz, Irina Shelukhina, Raisa Giniatullina, Fatma Tore, Boris V Safronov, Rashid Giniatullin
Serotonergic mechanisms play a central role in migraine pathology. However, the region-specific effects of serotonin (5-HT) mediated via multiple types of receptors in the nociceptive system are poorly understood. Using extracellular and patch-clamp recordings, we studied the action of 5-HT on the excitability of peripheral and central terminals of trigeminal afferents. 5-HT evoked long-lasting TTX-sensitive firing in the peripheral terminals of meningeal afferents, the origin site of migraine pain. Cluster analysis revealed that in majority of nociceptive fibers 5-HT induced either transient or persistent spiking activity with prevailing delta and theta rhythms...
December 23, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/28002451/investigating-the-potential-signaling-pathways-that-regulate-activation-of-the-novel-pkc-downstream-of-serotonin-in-aplysia
#15
Carole A Farah, Bryan Rourke, Unkyung Shin, Larissa Ferguson, María José Luna, Wayne S Sossin
Activation of the novel PKC Apl II in sensory neurons by serotonin (5HT) underlies the ability of 5HT to reverse synaptic depression, but the pathway from 5HT to PKC Apl II activation remains unclear. Here we find no evidence for the Aplysia-specific B receptors, or for adenylate cyclase activation, to translocate fluorescently-tagged PKC Apl II. Using an anti-PKC Apl II antibody, we monitor translocation of endogenous PKC Apl II and determine the dose response for PKC Apl II translocation, both in isolated sensory neurons and sensory neurons coupled with motor neurons...
2016: PloS One
https://www.readbyqxmd.com/read/27980071/a-pkm-generated-by-calpain-cleavage-of-a-classical-pkc-is-required-for-activity-dependent-intermediate-term-facilitation-in-the-presynaptic-sensory-neuron-of-aplysia
#16
Carole A Farah, Margaret H Hastings, Tyler W Dunn, Katrina Gong, Danay Baker-Andresen, Wayne S Sossin
Atypical PKM, a persistently active form of atypical PKC, is proposed to be a molecular memory trace, but there have been few examinations of the role of PKMs generated from other PKCs. We demonstrate that inhibitors used to inhibit PKMs generated from atypical PKCs are also effective inhibitors of other PKMs. In contrast, we demonstrate that dominant-negative PKMs show isoform-specificity. A dominant-negative PKM from the classical PKC Apl I blocks activity-dependent intermediate-term facilitation (a-ITF) when expressed in the sensory neuron, while a dominant-negative PKM from the atypical PKC Apl III does not...
January 2017: Learning & Memory
https://www.readbyqxmd.com/read/27965088/lanthionine-ketimine-ester-promotes-locomotor-recovery-after-spinal-cord-injury-by-reducing-neuroinflammation-and-promoting-axon-growth
#17
Ken Kotaka, Jun Nagai, Kenneth Hensley, Toshio Ohshima
The mammalian central nervous system (CNS) has limited regenerative ability after injury, largely due to scar formation and axonal growth inhibitors. Experimental suppression of neuroinflammation encourages recovery from spinal cord injury (SCI), yet practical means for pharmacologically treating SCI have remained elusive. Lanthionine ketimine (LK) is a natural brain sulfur amino acid metabolite with demonstrated anti-neuroinflammatory and neurotrophic activities. LK and its synthetic brain-penetrating ethyl ester (LKE) promote growth factor-dependent neurite extension in cultured cell and suppress microglial activation in animal models of neurodegeneration...
January 29, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27938441/a-dual-inhibitor-of-faah-and-trpv1-channels-shows-dose-dependent-effect-on-depression-like-behaviour-in-rats
#18
Christian Kirkedal, Gregers Wegener, Fabricio Moreira, Sâmia Regiane Lourenco Joca, Nico Liebenberg
OBJECTIVE: The cannabinoid receptor 1 (CB1) and transient receptor potential cation channel subfamily V member 1 (TRPV1) are proposed to mediate opposite behavioural responses. Their common denominator is the endocannabinoid ligand anandamide (AEA), which is believed to mediate antidepressant-like effect via CB1-R stimulation and depressive-like effect via TRPV1 activation. This is supposed to explain the bell-shaped dose-response curve for anandamide in preclinical models. METHODS: We investigated this assumption by administering the dual inhibitor of AEA hydrolysis and TRPV1 activation N-arachidonoyl-serotonin (AA-5HT) into the medial prefrontal cortex of rats...
December 12, 2016: Acta Neuropsychiatrica
https://www.readbyqxmd.com/read/27898075/maternal-high-fat-diet-prevents-developmental-programming-by-early-life-stress
#19
M Rincel, A L Lépinay, P Delage, J Fioramonti, V S Théodorou, S Layé, M Darnaudéry
Anxiety disorders and depression are well-documented in subjects exposed to adverse childhood events. Recently, maternal obesity and/or maternal consumption of high-fat diets (HFD) have been also proposed as risk factors for offspring mental health. Here using an animal model in rats, we explored the combinatorial effects of a maternal HFD (40% of energy from fat without impact on maternal weight; during gestation and lactation) and maternal separation (MS) in offspring. In the prefrontal cortex (PFC) of pups, MS led to changes in the expression of several genes such as Bdnf (brain derived neurotrophic factor), 5HT-r1a (serotonin receptor 1a) and Rest4 (neuron-restrictive silencer element, repressor element 1, silencing transcription factor (Rest), splicing variant 4)...
November 29, 2016: Translational Psychiatry
https://www.readbyqxmd.com/read/27898069/clozapine-modifies-the-differentiation-program-of-human-adipocytes-inducing-browning
#20
E Kristóf, Q-M Doan-Xuan, A K Sárvári, Á Klusóczki, P Fischer-Posovszky, M Wabitsch, Z Bacso, P Bai, Z Balajthy, L Fésüs
Administration of second-generation antipsychotic drugs (SGAs) often leads to weight gain and consequent cardio-metabolic side effects. We observed that clozapine but not six other antipsychotic drugs reprogrammed the gene expression pattern of differentiating human adipocytes ex vivo, leading to an elevated expression of the browning marker gene UCP1, more and smaller lipid droplets and more mitochondrial DNA than in the untreated white adipocytes. Laser scanning cytometry showed that up to 40% of the differentiating single primary and Simpson-Golabi-Behmel syndrome (SGBS) adipocytes had the characteristic morphological features of browning cells...
November 29, 2016: Translational Psychiatry
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