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https://www.readbyqxmd.com/read/28324647/metabolism-and-distribution-of-clozapine-n-oxide-implications-for-nonhuman-primate-chemogenetics
#1
Jessica Raper, J Scott Daniels, Ryan D Morrison, Leonard Howell, Jocelyne Bachevalier, Thomas Wichmann, Adriana Galvan
The use of Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) in neuroscience has rapidly expanded in rodent studies, but has lagged behind in nonhuman primate (NHP) experiments, slowing the development of this method for therapeutic use in humans. One reason for the slow adoption of DREADD technology in primates is that the pharmacokinetic properties and bioavailability of clozapine-n-oxide (CNO), the most commonly used ligand for human muscarinic (hM) DREADDs, are not fully described in primates...
March 21, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28324197/the-spectrum-of-magnetic-resonance-findings-in-cerebrotendinous-xanthomatosis-redefinition-and-evidence-of-new-markers-of-disease-progression
#2
Andrea Mignarri, Maria Teresa Dotti, Antonio Federico, Nicola De Stefano, Marco Battaglini, Irene Grazzini, Paolo Galluzzi, Lucia Monti
Cerebrotendinous xanthomatosis (CTX) is a metabolic disease characterized by systemic signs and neurological impairment, which can be prevented if chenodeoxycholic acid (CDCA) treatment is started early. Despite brain MRI represents an essential diagnostic tool, the spectrum of findings is worth to be reappraised, and follow-up data are needed. We performed clinical evaluation and brain MRI in 38 CTX patients. Sixteen of them who were untreated at baseline examination underwent clinical and MRI follow-up after long-term treatment with CDCA...
March 21, 2017: Journal of Neurology
https://www.readbyqxmd.com/read/28324191/planarian-homolog-of-puromycin-sensitive-aminopeptidase-djpsa-is-required-for-brain-regeneration
#3
Suge Wu, Bin Liu, Zuoqing Yuan, Xiufang Zhang, Hong Liu, Qiuxiang Pang, Bosheng Zhao
Puromycin-sensitive aminopeptidase (PSA) belongs to the M1 zinc metallopeptidase family. PSA is the most abundant aminopeptidase in the brain and plays a role in the metabolism of neuropeptides including those involved in neurodegeneration. A cDNA DjPsa was identified from the planarian Dugesia japonica cDNA library. It contains a 639-bp open reading frame corresponding to a deduced protein of 212 amino acids. Whole mount in situ hybridization revealed that DjPsa is expressed in the brain and ventral nerve cords of intact and regenerating animals and demonstrates a tissue and stage-specific expression pattern of DjPsa in developing embryos and larvae...
June 2017: Invertebrate Neuroscience: IN
https://www.readbyqxmd.com/read/28324109/sex-specific-life-course-changes-in-the-neuro-metabolic-phenotype-of-glut3-null-heterozygous-mice-ketogenic-diet-ameliorates-electroencephalographic-seizures-and-improves-sociability
#4
Yun Dai, Yuanzi Zhao, Masatoshi Tomi, Bo-Chul Shin, Shanthie Thamotharan, Andrey Mazarati, Raman Sankar, Elizabeth A Wang, Carlos Cepeda, Michael S Levine, Jingjing Zhang, Andrew Frew, Jeffry R Alger, Peter Clark, Monica Sondhi, Sudatip Kositamongkol, Leah Leibovitch, Sherin U Devaskar
We tested the hypothesis that exposure of glut3+/- mice to a ketogenic diet ameliorates autism-like features which includes aberrant behavior and electrographic seizures. We first investigated the life course sex-specific changes in basal plasma-CSF-brain metabolic profile, brain glucose transport/uptake, glucose and monocarboxylate transporter proteins, and ATP in the presence or absence of systemic insulin administration. Glut3+/- male but not female mice (5m of age) displayed reduced CSF glucose/lactate concentrations with no change in brain Glut1, Mct2, glucose uptake or ATP...
January 24, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323986/chronic-intranasal-insulin-does-not-affect-hepatic-lipids-but-lowers-circulating-bcaas-in-healthy-male-subjects
#5
Thomas Scherer, Peter Wolf, Sabina Smajis, Melania Gaggini, Martina Hackl, Amalia Gastaldelli, Peter Klimek, Elisa Einwallner, Rodrig Marculescu, Anton Luger, Clemens Fürnsinn, Siegfried Trattnig, Christoph Buettner, Martin Krššák, Michael Krebs
Context: Non-alcoholic fatty liver disease and elevated circulating branched-chain amino acids (BCAAs) are common characteristics of obesity and type 2 diabetes. In rodents, brain insulin signaling controls both hepatic triglyceride secretion and BCAA catabolism. Whether brain insulin signaling controls similar metabolic pathways in humans is unknown. Objective: Here we assessed if intranasal insulin, a method to preferentially deliver insulin to the central nervous system, is able to modulate hepatic lipid content and plasma BCAAs in humans...
January 16, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28323958/jmjd3-is-crucial-for-female-avpv-rip-cre-neuron-controlled-kisspeptin-estrogen-feedback-loop-and-reproductive-function
#6
Anying Song, Shujun Jiang, Qinghua Wang, Jianghuan Zou, Zhaoyu Lin, Xiang Gao
The hypothalamic-pituitary-gonadal axis controls development, reproduction, and metabolism. While most studies were focusing on the hierarch from brain to gonad, many questions remain unresolved concerning the feedback from gonad to the central nervous system, especially on the potential epigenetic modification in hypothalamic neurons. In this report, we generated genetically modified mice lacking histone H3 lysine 27 demethylase JMJD3 in hypothalamic RIP-Cre neurons. The female mutant mice display late-onset obesity due to reduced locomotor activity and decreased energy expenditure...
March 9, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323825/association-between-fatty-acid-metabolism-in-the-brain-and-alzheimer-disease-neuropathology-and-cognitive-performance-a-nontargeted-metabolomic-study
#7
Stuart G Snowden, Amera A Ebshiana, Abdul Hye, Yang An, Olga Pletnikova, Richard O'Brien, John Troncoso, Cristina Legido-Quigley, Madhav Thambisetty
BACKGROUND: The metabolic basis of Alzheimer disease (AD) pathology and expression of AD symptoms is poorly understood. Omega-3 and -6 fatty acids have previously been linked to both protective and pathogenic effects in AD. However, to date little is known about how the abundance of these species is affected by differing levels of disease pathology in the brain. METHODS AND FINDINGS: We performed metabolic profiling on brain tissue samples from 43 individuals ranging in age from 57 to 95 y old who were stratified into three groups: AD (N = 14), controls (N = 14) and "asymptomatic Alzheimer's disease" (ASYMAD), i...
March 2017: PLoS Medicine
https://www.readbyqxmd.com/read/28323671/codeine-and-opioid-metabolism-implications-and-alternatives-for-pediatric-pain-management
#8
Vidya Chidambaran, Senthilkumar Sadhasivam, Mohamed Mahmoud
PURPOSE OF REVIEW: Use of perioperative opioids for surgical pain management of children presents clinical challenges because of concerns of serious adverse effects including life-threatening respiratory depression. This is especially true for children with history of obstructive sleep apnea. This review will explore current knowledge of clinically relevant factors and genetic polymorphisms that affect opioid metabolism and postoperative outcomes in children. RECENT FINDINGS: Within the past several years, an increasing number of case reports have illustrated clinically important respiratory depression, anoxic brain injuries and even death among children receiving appropriate weight-based dosages of codeine and other opioids for analgesia at home setting particularly following tonsillectomy...
March 18, 2017: Current Opinion in Anaesthesiology
https://www.readbyqxmd.com/read/28323516/does-normobaric-hyperoxia-cause-oxidative-stress-in-the-injured-brain-a-microdialysis-study-using-8-iso-pgf2%C3%AE-as-a-biomarker
#9
Marian Vidal-Jorge, Angela Sánchez-Guerrero, Gemma Mur-Bonet, Lidia Castro, Andreea Rădoi, Marilyn Riveiro, Natividad Fernández-Prado, Jacinto Baena, Maria A Poca, Juan Sahuquillo
Significant controversy exists regarding the potential clinical benefit of normobaric hyperoxia therapy (NBO) in patients with traumatic brain injury (TBI). This study consisted of two aims: 1) to assess whether NBO improves brain oxygenation and metabolism and 2) to determine whether this therapy may increase the risk of oxidative stress (OxS), using 8-iso-PGF2α as a biomarker. Thirty-one patients with a median admission Glasgow Coma Scale score of 4 (min: 3, max: 12) were monitored with cerebral microdialysis and brain tissue oxygen sensors and treated with FiO2 of 1...
March 21, 2017: Journal of Neurotrauma
https://www.readbyqxmd.com/read/28320134/post-hemorrhagic-hydrocephalus-recent-advances-and-new-therapeutic-insights
#10
REVIEW
Qianwei Chen, Zhou Feng, Qiang Tan, Jing Guo, Jun Tang, Liang Tan, Hua Feng, Zhi Chen
Post-hemorrhagic hydrocephalus (PHH), also referred to as progressive ventricular dilatation, is caused by disturbances in cerebrospinal fluid (CSF) flow or absorption following hemorrhage in the brain. As one of the most serious complications of neonatal/adult intraventricular hemorrhage (IVH), subarachnoid hemorrhage (SAH), and traumatic brain injury (TBI), PHH is associated with increased morbidity and disability of these events. Common sequelae of PHH include neurocognitive impairment, motor dysfunction, and growth impairment...
April 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28319610/capillary-k-sensing-initiates-retrograde-hyperpolarization-to-increase-local-cerebral-blood-flow
#11
Thomas A Longden, Fabrice Dabertrand, Masayo Koide, Albert L Gonzales, Nathan R Tykocki, Joseph E Brayden, David Hill-Eubanks, Mark T Nelson
Blood flow into the brain is dynamically regulated to satisfy the changing metabolic requirements of neurons, but how this is accomplished has remained unclear. Here we demonstrate a central role for capillary endothelial cells in sensing neural activity and communicating it to upstream arterioles in the form of an electrical vasodilatory signal. We further demonstrate that this signal is initiated by extracellular K(+) -a byproduct of neural activity-which activates capillary endothelial cell inward-rectifier K(+) (KIR2...
March 20, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28319562/translating-biomarkers-from-research-to-clinical-use-in-pediatric-neurocritical-care-focus-on-traumatic-brain-injury-and-cardiac-arrest
#12
Andrew J Prout, Michael S Wolf, Ericka L Fink
PURPOSE OF REVIEW: Traumatic brain injury (TBI) and cardiac arrest are important causes of morbidity and mortality in children. Improved diagnosis and outcome prognostication using validated biomarkers could allow clinicians to better tailor therapies for optimal efficacy. RECENT FINDINGS: Contemporary investigation has yielded plentiful biomarker candidates of central nervous system (CNS) injury, including macromolecules, genetic, inflammatory, oxidative, and metabolic biomarkers...
March 17, 2017: Current Opinion in Pediatrics
https://www.readbyqxmd.com/read/28319103/microglia-activation-due-to-obesity-programs-metabolic-failure-leading-to-type-two-diabetes
#13
REVIEW
R Maldonado-Ruiz, L Montalvo-Martínez, L Fuentes-Mera, A Camacho
Obesity is an energy metabolism disorder that increases susceptibility to the development of metabolic diseases. Recently, it has been described that obese subjects have a phenotype of chronic inflammation in organs that are metabolically relevant for glucose homeostasis and energy. Altered expression of immune system molecules such as interleukins IL-1, IL-6, IL-18, tumor necrosis factor alpha (TNF-α), serum amyloid A (SAA), and plasminogen activator inhibitor-1 (PAI-1), among others, has been associated with the development of chronic inflammation in obesity...
March 20, 2017: Nutrition & Diabetes
https://www.readbyqxmd.com/read/28318994/more-flavor-for-flavonoid-based-interventions
#14
Nadeem O Kaakoush, Margaret J Morris
Poor diets are associated with obesity and a decline in cognitive function. Flavonoids are plant compounds that have been associated with improved metabolic parameters in obesity and reversal of cognitive decline. Given that microbial flavonoid conversion is important for bioactivity, flavonoid-derived neuroactive compounds may be functionally crucial in the gut microbiome-brain axis.
March 17, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28318543/obesity-induced-neuroinflammation-beyond-the-hypothalamus
#15
REVIEW
Owein Guillemot-Legris, Giulio G Muccioli
Obesity is now a worldwide health issue. Far from being limited to weight gain, obesity is generally associated with low-grade inflammation and with a cluster of disorders collectively known as the 'metabolic syndrome'. When considering obesity and the subsequent neuroinflammation, the focus was long set on the hypothalamus. More recently, obesity-derived neuroinflammation has been shown to affect other brain structures such as the hippocampus, cortex, brainstem, or amygdala. Furthermore, obesity has been associated with increased occurrence of central disorders such as depression and impaired cognitive function...
March 16, 2017: Trends in Neurosciences
https://www.readbyqxmd.com/read/28318368/the-wayward-methyl-group-and-the-cascade-to-cancer
#16
Robert M Hoffman
We propose here a hypothesis of the cause of cancer that brings together fundamental changes in methyl-group metabolism resulting in global DNA hypomethylation which destabilizes the genome leading to aneuploid karyotypes which evolve and stabilize into autonomous cancer. Experimental support for this hypothesis is that methioine dependence is a general metabolic defect in caner. Methionine dependence is due to excess use of methionene for aberrant transmethylation reactions that apparently divert methyl groups from DNA...
March 20, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28317648/clinical-validity-of-brain-fluorodeoxyglucose-positron-emission-tomography-as-a-biomarker-for-alzheimer-s-disease-in-the-context-of-a-structured-5-phase-development-framework
#17
REVIEW
Valentina Garibotto, Karl Herholz, Marina Boccardi, Agnese Picco, Andrea Varrone, Agneta Nordberg, Flavio Nobili, Osman Ratib
The use of Alzheimer's disease (AD) biomarkers is supported in diagnostic criteria, but their maturity for clinical routine is still debated. Here, we evaluate brain fluorodeoxyglucose positron emission tomography (FDG PET), a measure of cerebral glucose metabolism, as a biomarker to identify clinical and prodromal AD according to the framework suggested for biomarkers in oncology, using homogenous criteria with other biomarkers addressed in parallel reviews. FDG PET has fully achieved phase 1 (rational for use) and most of phase 2 (ability to discriminate AD subjects from healthy controls or other forms of dementia) aims...
April 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28317485/defective-insulin-signalling-mediated-by-inflammation-connects-obesity-to-alzheimer-disease-relevant-pharmacological-therapies-and-preventive-dietary-interventions
#18
Arantxa Rodriguez-Casado, Adolfo Toledano-Díaz, Adolfo Toledano
Recent evidence suggests that obesity, besides being a risk factor for cardiovascular events, also increases the risk of Alzheimer's disease. Insulin resistance is common in all cases of obesity and appears to be the linkage between both diseases. Obesity, often associated with excessive fat and sugar intake, represents a preclinical stage toward insulin resistance during which nutrition intervention is likely to have maximum effect. In this way, healthy lifestyles lifetime to prevent obesity-related modifiable risk factors such as inflammation, oxidative stress and metabolic disorders could be simultaneously beneficial for preserving cognition and controlling the Alzheimer's...
March 16, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28317427/fatigue-is-it-all-neurochemistry
#19
Romain Meeusen, Bart Roelands
Fatigue during exercise can be approached from different angles. Peripheral fatigue is usually described as an impairment located in the muscle and characterized by a metabolic end point, while central fatigue is defined as a failure of the central nervous system to adequately drive the muscle. The aim of the present narrative review paper is to look at the mechanisms involved in the occurrence of fatigue during prolonged exercise, predominantly from a brain neurochemical point of view. From studies in rodents it is clear that exercise increases the release of several neurotransmitters in different brain regions, and that the onset of fatigue can be manipulated when dopaminergic influx in the preoptic and anterior hypothalamus is increased, interfering with thermoregulation...
March 19, 2017: European Journal of Sport Science
https://www.readbyqxmd.com/read/28317246/brain-gene-expression-is-influenced-by-incubation-temperature-during-leopard-gecko-eublepharis-macularius-development
#20
Maria Michela Pallotta, Mimmo Turano, Raffaele Ronca, Marcello Mezzasalma, Agnese Petraccioli, Gaetano Odierna, Teresa Capriglione
Sexual differentiation (SD) during development results in anatomical, metabolic, and physiological differences that involve not only the gonads, but also a variety of other biological structures, such as the brain, determining differences in morphology, behavior, and response in the breeding season. In many reptiles, whose sex is determined by egg incubation temperature, such as the leopard gecko, Eublepharis macularius, embryos incubated at different temperatures clearly differ in the volume of brain nuclei that modulate behavior...
March 20, 2017: Journal of Experimental Zoology. Part B, Molecular and Developmental Evolution
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