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https://www.readbyqxmd.com/read/29236160/ethanol-and-cytokines-in-the-central-nervous-system
#1
Marisa Roberto, Reesha R Patel, Michal Bajo
The innate immune system plays a critical role in the ethanol-induced neuroimmune response in the brain. Ethanol initiates the innate immune response via activation of the innate immune receptors Toll-like receptors (TLRs, e.g., TLR4, TLR3, TLR7) and NOD-like receptors (inflammasome NLRs) leading to a release of a plethora of chemokines and cytokines and development of the innate immune response. Cytokines and chemokines can have pro- or anti-inflammatory properties through which they regulate the immune response...
December 14, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/29235904/molecular-modeling-and-docking-studies-of-the-oxytocin-receptor
#2
Gloria Antobreh, Istvan Enyedy, Aina Westrheim Ravna
AIM: Low oxytocin (OT) level is involved in a number of psychiatric diseases, indicating that OT could be used to aid treating these disorders. OT itself is unable to cross the blood-brain barrier, and development of new small nonpeptide drugs targeting the OT receptor (OXTR) may be beneficial for treating mental disorders. Results & methodology: Three OXTR models were constructed based on crystallized homologous proteins (Protein Data Bank [PDB]: 2Y00, PDB: 4BVN and PDB: 4LDE). The abilities of the models to discriminate between true binders and decoys were analyzed using receiver operating characteristics curves, and the 4LDE-based model gave the best result...
December 13, 2017: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/29235880/a-critical-review-of-physicochemical-properties-and-analytical-methods-applied-to-quantitative-determination-of-ebastine
#3
Rafael Giorgetti Frare, Anil Kumar Singh
Allergic diseases are the most common conditions in children and the second most frequent in adults. Currently, there are two well-defined generations of antihistamines, those belonging to first generation, with inherent side effects such as drowsiness and anticholinergic effects. These side effects are often attributed to their high lipophilicity and high affinity for brain H1 receptors. The ebastine is a modern antihistaminic drug belongs to the second generation and has lower lipophilicity, which diminish the undesirable side effects...
December 13, 2017: Critical Reviews in Analytical Chemistry
https://www.readbyqxmd.com/read/29235509/in-vivo-metabolic-imaging-of-traumatic-brain-injury
#4
Caroline Guglielmetti, Austin Chou, Karen Krukowski, Chloe Najac, Xi Feng, Lara-Kirstie Riparip, Susanna Rosi, Myriam M Chaumeil
Complex alterations in cerebral energetic metabolism arise after traumatic brain injury (TBI). To date, methods allowing for metabolic evaluation are highly invasive, limiting our understanding of metabolic impairments associated with TBI pathogenesis. We investigated whether 13C MRSI of hyperpolarized (HP) [1-13C] pyruvate, a non-invasive metabolic imaging method, could detect metabolic changes in controlled cortical injury (CCI) mice (n = 57). Our results show that HP [1-13C] lactate-to-pyruvate ratios were increased in the injured cortex at acute (12/24 hours) and sub-acute (7 days) time points after injury, in line with decreased pyruvate dehydrogenase (PDH) activity, suggesting impairment of the oxidative phosphorylation pathway...
December 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29235461/oxytocin-enhances-observational-fear-in-mice
#5
Marc T Pisansky, Leah R Hanson, Irving I Gottesman, Jonathan C Gewirtz
Empathy is fundamental to human relations, but its neural substrates remain largely unknown. Here we characterize the involvement of oxytocin in the capacity of mice to display emotional state-matching, an empathy-like behavior. When exposed to a familiar conspecific demonstrator in distress, an observer mouse becomes fearful, as indicated by a tendency to freeze and subsequent efforts to escape. Both intranasal oxytocin administration and chemogenetic stimulation of oxytocin neurons render males sensitive to the distress of an unfamiliar mouse...
December 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/29235097/activation-of-astrocytic-par1-receptors-in-the-rat-nucleus-of-the-solitary-tract-regulates-breathing-through-modulation-of-presynaptic-trpv1
#6
Rafiq Huda, Zheng Chang, Jeehaeh Do, Donald R McCrimmon, Marco Martina
Many of the cellular and molecular mechanisms underlying astrocytic modulation of synaptic function remain poorly understood. Recent studies show that G-protein coupled receptor-mediated astrocyte activation modulates synaptic transmission in the nucleus of the solitary tract (NTS), a brainstem nucleus that regulates crucial physiological processes including cardiorespiratory activity. By using calcium imaging and patch clamp recordings in acute brain slices of wild-type and TRPV1-/- rats, we show that activation of proteinase-activated receptor 1 (PAR-1) in NTS astrocytes potentiates presynaptic glutamate release on NTS neurons...
December 12, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/29234276/functional-reintegration-of-sensory-neurons-and-transitional-dendritic-reduction-of-mitral-tufted-cells-during-injury-induced-recovery-of-the-larval-xenopus-olfactory-circuit
#7
Sara J Hawkins, Lukas Weiss, Thomas Offner, Katarina Dittrich, Thomas Hassenklöver, Ivan Manzini
Understanding the mechanisms involved in maintaining lifelong neurogenesis has a clear biological and clinical interest. In the present study, we performed olfactory nerve transection on larval Xenopus to induce severe damage to the olfactory circuitry. We surveyed the timing of the degeneration, subsequent rewiring and functional regeneration of the olfactory system following injury. A range of structural labeling techniques and functional calcium imaging were performed on both tissue slices and whole brain preparations...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29234141/cannabinoid-type-2-receptors-in-dopamine-neurons-inhibits-psychomotor-behaviors-alters-anxiety-depression-and-alcohol-preference
#8
Qing-Rong Liu, Ana Canseco-Alba, Hai-Ying Zhang, Patricia Tagliaferro, Monika Chung, Eugene Dennis, Branden Sanabria, Norman Schanz, Joao Carlos Escosteguy-Neto, Hiroki Ishiguro, Zhicheng Lin, Susan Sgro, Claire M Leonard, Jair Guilherme Santos-Junior, Eliot L Gardner, Josephine M Egan, Jeung Woon Lee, Zheng-Xiong Xi, Emmanuel S Onaivi
Cannabinoid CB2 receptors (CB2Rs) are expressed in mouse brain dopamine (DA) neurons and are involved in several DA-related disorders. However, the cell type-specific mechanisms are unclear since the CB2R gene knockout mice are constitutive gene knockout. Therefore, we generated Cnr2-floxed mice that were crossed with DAT-Cre mice, in which Cre- recombinase expression is under dopamine transporter gene (DAT) promoter control to ablate Cnr2 gene in midbrain DA neurons of DAT-Cnr2 conditional knockout (cKO) mice...
December 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29233969/receptor-interacting-protein-140-as-a-co-repressor-of-heat-shock-factor-1-regulates-neuronal-stress-response
#9
Yu-Lung Lin, Hong-Chieh Tsai, Pei-Yao Liu, Michael Benneyworth, Li-Na Wei
Heat shock response (HSR) is a highly conserved transcriptional program that protects organisms against various stressful conditions. However, the molecular mechanisms modulating HSR, especially the suppression of HSR, is poorly understood. Here, we found that RIP140, a wide-spectrum cofactor of nuclear hormone receptors, acts as a co-repressor of heat shock factor 1 (HSF1) to suppress HSR in healthy neurons. When neurons are stressed such as by heat shock or sodium arsenite (As), cells engage specific proteosome-mediated degradation to reduce RIP140 level, thereby relieving the suppression and activating HSR...
December 12, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29233934/chronic-infusion-of-taurolithocholate-into-the-brain-increases-fat-oxidation-in-mice
#10
Hannah M Eggink, Lauren L Tambyrajah, Rosa van den Berg, Isabel Mol, Jose K van den Heuvel, Martijn Koehorst, Albert K Groen, Anita Boelen, Andries Kalsbeek, Johannes A Romijn, Patrick C N Rensen, Sander Kooijman, Maarten R Soeters
Bile acids can function in the postprandial state as circulating signaling molecules in the regulation of glucose and lipid metabolism via the transmembrane receptor TGR5 and nuclear receptor FXR. Both receptors are present in the central nervous system, but their function in the brain is unclear. Therefore, we investigated the effects of intracerebroventricular (icv) administration of taurolithocholate (tLCA), a strong TGR5 agonist, and GW4064, a synthetic FXR agonist, on energy metabolism. We determined the effects of chronic icv infusion of tLCA, GW4064, or vehicle on energy expenditure, body weight and composition as well as tissue specific fatty acid uptake in mice equipped with osmotic minipumps...
December 12, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/29233654/trophic-modulation-of-gamma-oscillations-the-key-role-of-processing-protease-for-neuregulin-1-and-bdnf-precursors
#11
Hideki Tamura, Sadao Shiosaka, Shota Morikawa
Gamma oscillations within the cerebral cortex and hippocampus are associated with cognitive processes, including attention, sensory perception, and memory formation; a deficit in gamma regulation is a common symptom of neurologic and psychiatric disorders. Accumulating evidence has suggested that gamma oscillations result from the synchronized activity of cell assemblies coordinated mainly by parvalbumin-positive inhibitory interneurons. The modulator molecules for parvalbumin-positive interneurons are major research targets and have the potential to control the specific oscillatory rhythm and behavior originating from neural coordination...
December 9, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/29233636/amylin-in-alzheimer-s-disease-pathological-peptide-or-potential-treatment
#12
REVIEW
Elizabeth G Mietlicki-Baase
Alzheimer's disease (AD) is a neurodegenerative disease for which we currently lack effective treatments or a cure. The pancreatic peptide hormone amylin has recently garnered interest as a potential pharmacological target for the treatment of AD. A number of studies have demonstrated that amylin and amylin analogs like the FDA-approved diabetes drug pramlintide can reduce amyloid burden in the brain and improve cognitive symptoms of AD. However, other data suggest that amylin may have pathological effects in AD due to its propensity to misfold and aggregate under certain conditions...
December 9, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29233264/imaging-the-glutamate-receptor-subtypes-much-achieved-and-still-much-to-do
#13
REVIEW
Stefan Gruber, Simon M Ametamey
Functional imaging of glutamate receptors using PET imaging modality can be used to study numerous CNS disorders and also to select appropriate doses of clinically relevant glutamate-receptor-targeting candidate drugs. Great strides have been made in developing PET imaging probes for the non-invasive detection of glutamate receptors in the brain. This review highlights recent progress made towards the development of glutamatergic PET imaging agents. Focus is placed on PET imaging probes that have been labelled with either carbon-11 or fluorine-18...
November 2017: Drug Discovery Today. Technologies
https://www.readbyqxmd.com/read/29233198/clinical-efficacy-and-safety-of-switch-from-bosentan-to-macitentan-in-children-and-young-adults-with-pulmonary-arterial-hypertension
#14
Ebru Aypar, Dursun Alehan, Tevfik Karagöz, Hayrettin Hakan Aykan, İlker Ertugrul
BACKGROUND: Macitentan is an orally active, potent, dual endothelin receptor antagonist and is the only registered treatment for pulmonary arterial hypertension that significantly reduced morbidity and mortality in a long-term event-driven study. Aim Few studies compared the clinical efficacy and safety of switch from bosentan to macitentan only in adult patients with pulmonary arterial hypertension. We aimed to evaluate the clinical efficacy and safety of switch from bosentan to macitentan in children and young adults...
December 13, 2017: Cardiology in the Young
https://www.readbyqxmd.com/read/29233099/pronounced-strain-specific-chemosensory-receptor-gene-expression-in-the-mouse-vomeronasal-organ
#15
Kyle Duyck, Vasha DuTell, Limei Ma, Ariel Paulson, C Ron Yu
BACKGROUND: The chemosensory system plays an important role in orchestrating sexual behaviors in mammals. Pheromones trigger sexually dimorphic behaviors and different mouse strains exhibit differential responses to pheromone stimuli. It has been speculated that differential gene expression in the sensory organs that detect pheromones may underlie sexually-dimorphic and strain-specific responses to pheromone cues. RESULTS: We have performed transcriptome analyses of the mouse vomeronasal organ, a sensory organ recognizing pheromones and interspecies cues...
December 12, 2017: BMC Genomics
https://www.readbyqxmd.com/read/29232839/agarwood-essential-oil-displays-sedative-hypnotic-effects-through-the-gabaergic-system
#16
Shuai Wang, Canhong Wang, Deqian Peng, Xinmin Liu, Chongming Wu, Peng Guo, Jianhe Wei
Although agarwood has been used as a tranquilizer in Asian countries for hundreds of years, the underlying pharmacological basis is still unclear. This study investigated the sedative-hypnotic effect of agarwood essential oil (AEO) using locomotor activity and pentobarbital-induced sleeping assays in mice. Single (1-day) and multiple (7- and 14-days) administrations of 60 mg/kg AEO generated significant sedative effect on inhibiting locomotor activity and hypnotic effect on pentobarbital-induced sleeping in mice...
December 9, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29232411/rev-erb-agonist-improves-adverse-cardiac-remodeling-and-survival-in-myocardial-infarction-through-an-anti-inflammatory-mechanism
#17
Endin Nokik Stujanna, Nobuyuki Murakoshi, Kazuko Tajiri, DongZhu Xu, Taizo Kimura, Rujie Qin, Duo Feng, Saori Yonebayashi, Yukino Ogura, Fumi Yamagami, Akira Sato, Akihiko Nogami, Kazutaka Aonuma
Rev-erb α, known as nuclear receptor 1D1 (NR1D1), regulates circadian rhythm, modulates glucose and lipid metabolism, and inflammatory response. However, little is known about the effect of Rev-erb agonist on the progression of myocardial infarction (MI) and heart failure. To investigate it, wild-type male mice underwent sham-operation or permanent ligation of the left anterior descending coronary artery to create MI model. Rev-erb agonist SR9009 (100 mg/kg/day) or vehicle was intraperitoneally administered...
2017: PloS One
https://www.readbyqxmd.com/read/29232014/mutations-of-the-glycine-cleavage-system-genes-possibly-affect-the-negative-symptoms-of-schizophrenia-through-metabolomic-profile-changes
#18
Akane Yoshikawa, Fumichika Nishimura, Aya Inai, Yosuke Eriguchi, Masaki Nishioka, Atsuhiko Takaya, Mamoru Tochigi, Yoshiya Kawamura, Tadashi Umekage, Kayoko Kato, Tsukasa Sasaki, Yoshiaki Ohashi, Kazuya Iwamoto, Kiyoto Kasai, Chihiro Kakiuchi
AIM: Hypofunction of N-methyl-D-aspartate receptors (NMDARs) may contribute to the pathophysiology of schizophrenia (SCZ). Recently, the glycine cleavage system (GCS) was shown to affect NMDAR function in the brain. GCS functional defects cause nonketotic hyperglycinemia (NKH), the atypical phenotype of which presents psychiatric symptoms similar to SCZ. Here, we examined the involvement of GCS in SCZ. METHODS: First, to identify the rare variants and the exonic deletions, we re-sequenced all the coding exons and the splice sites of four GCS genes (GLDC, AMT, GCSH, DLD) in 474 patients with SCZ and 475 controls and performed multiplex ligation-dependent probe amplification (MLPA) analysis in SCZ...
December 12, 2017: Psychiatry and Clinical Neurosciences
https://www.readbyqxmd.com/read/29231924/the-mineralocorticoid-receptor-knockout-in-medaka-is-further-validated-by-glucocorticoid-receptor-compensation
#19
Tatsuya Sakamoto, Madoka Yoshiki, Hirotaka Sakamoto
To study the critical role of mineralocorticoid signalling, we generated a constitutive mineralocorticoid receptor (MR)-knockout (KO) medaka as the first adult-viable MR-KO animal. This KO medaka displayed abnormal behaviours affected by visual stimuli. In contrast, the loss of MR did not result in overt phenotypic changes in osmoregulation, despite the well-known osmoregulatory functions of MR in mammals. Since glucocorticoid receptor (GR) has been suggested to compensate for loss of MR, we examined expression of duplicated GRs with markedly different ligand sensitivities, in various tissues...
December 12, 2017: Scientific Data
https://www.readbyqxmd.com/read/29231773/molecular-imaging-of-autism-spectrum-disorder
#20
Brian Jaeho Hwang, Mona Adel Mohamed, James Robert Brašić
Autism spectrum disorder (ASD) is a condition with onset in early childhood characterized by marked deficits in interpersonal interactions and communication and by a restricted and repetitive range of interests and activities. This review points out key recent findings utilizing molecular imaging including magnetic resonance spectroscopy (MRS) and nuclear neuroimaging techniques such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT). MRS indicates an excitatory/inhibitory imbalance in high-functioning autism...
December 12, 2017: International Review of Psychiatry
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