rudyvdbrink/CitationDatabase huggingface dataset:
Significance of neuronal cytochrome P450 activity in opioid-mediated stress-induced analgesia.
Brain research, 2014

Stressful environmental changes can suppress nociceptive transmission, a phenomenon known as "stress-induced analgesia". Depending on the stressor and the subject, opioid or non-opioid mechanisms are activated. Brain μ opioid receptors mediate analgesia evoked either by exogenous agents (e.g. morphine), or by the release of endogenous opioids following stressful procedures. Recent work with morphine and neuronal cytochrome P450 (P450)-deficient mice proposed a signal transduction role for P450 enzymes in µ analgesia. Since µ opioid receptors also mediate some forms of stress-induced analgesia, the present studies assessed the significance of brain P450 activity in opioid-mediated stress-induced analgesia. Two widely-used models of opioid stress-induced analgesia (restraint and warm water swim) were studied in both sexes of wild-type control and P450-deficient (Null) mice. In control mice, both stressors evoked moderate analgesic responses which were blocked by pretreatment with the opioid antagonist naltrexone, confirming the opioid nature of these responses. Consistent with literature, sex differences (control female>control male) were seen in swim-induced, but not restraint-induced, analgesia. Null mice showed differential responses to the two stress paradigms. As compared with control subjects, Null mice showed highly attenuated restraint-induced analgesia, showing a critical role for neuronal P450s in this response. However, warm water swim-induced analgesia was unchanged in Null vs. control mice. Additional control experiments confirmed the absence of morphine analgesia in Null mice. These results are the first to show that some forms of opioid-mediated stress-induced analgesia require brain neuronal P450 activity.
Clinical trial methodologies for disease-modifying therapeutic approaches.
Neurobiology of aging, 2011

In recent years, advances in Alzheimer's disease (AD) biomarker research have provided powerful tools to improve trial design. In particular, biomarkers provide powerful methods for the selection of individuals with Alzheimer's disease prior to the onset of dementia. Data suggest that neuroimaging biomarkers will be useful as endpoints for trials in very early, even asymptomatic disease, though further work is necessary to establish validity for regulatory purposes.
Intervention against hypertension in the next generation programmed by developmental hypoxia.
PLoS biology, 2019

Evidence derived from human clinical studies and experimental animal models shows a causal relationship between adverse pregnancy and increased cardiovascular disease in the adult offspring. However, translational studies isolating mechanisms to design intervention are lacking. Sheep and humans share similar precocial developmental milestones in cardiovascular anatomy and physiology. We tested the hypothesis in sheep that maternal treatment with antioxidants protects against fetal growth restriction and programmed hypertension in adulthood in gestation complicated by chronic fetal hypoxia, the most common adverse consequence in human pregnancy. Using bespoke isobaric chambers, chronically catheterized sheep carrying singletons underwent normoxia or hypoxia (10% oxygen [O2]) ± vitamin C treatment (maternal 200 mg.kg-1 IV daily) for the last third of gestation. In one cohort, the maternal arterial blood gas status, the value at which 50% of the maternal hemoglobin is saturated with oxygen (P50), nitric oxide (NO) bioavailability, oxidative stress, and antioxidant capacity were determined. In another, naturally delivered offspring were raised under normoxia until early adulthood (9 months). Lambs were chronically instrumented and cardiovascular function tested in vivo. Following euthanasia, femoral arterial segments were isolated and endothelial function determined by wire myography. Hypoxic pregnancy induced fetal growth restriction and fetal oxidative stress. At adulthood, it programmed hypertension by enhancing vasoconstrictor reactivity and impairing NO-independent endothelial function. Maternal vitamin C in hypoxic pregnancy improved transplacental oxygenation and enhanced fetal antioxidant capacity while increasing NO bioavailability, offsetting constrictor hyper-reactivity and replenishing endothelial function in the adult offspring. These discoveries provide novel insight into mechanisms and interventions against fetal growth restriction and adult-onset programmed hypertension in an animal model of complicated pregnancy in a species of similar temporal developmental milestones to humans.
Proceedings of the Sleep and Epilepsy Workshop: Section 1 Decreasing Seizures-Improving Sleep and Seizures, Themes for Future Research.
Epilepsy currents, 2021

Epileptic seizures, sleep, and circadian timing share bilateral interactions, but concerted work to characterize these interactions and to leverage them to the advantage of patients with epilepsy remains in beginning stages. To further the field, a multidisciplinary group of sleep physicians, epileptologists, circadian timing experts, and others met to outline the state of the art, gaps of knowledge, and suggest ways forward in clinical, translational, and basic research. A multidisciplinary panel of experts discussed these interactions, centered on whether improvements in sleep or circadian rhythms improve decrease seizure frequency. In addition, education about sleep was lacking in among patients, their families, and physicians, and that focus on education was an extremely important "low hanging fruit" to harvest. Improvements in monitoring technology, experimental designs sensitive to the rigor required to dissect sleep versus circadian influences, and clinical trials in seizure reduction with sleep improvements were appropriate.
Three dimensional model-based analysis of the lenticulostriate arteries and identification of the vessels correlated to the infarct area: preliminary results.
International journal of stroke : official journal of the International Stroke Society, 2012

Small vessel diseases have been studied noninvasively with magnetic resonance imaging. Direct observation or visualization of the connected microvessel to the infarct, however, was not possible due to the limited resolution. Hence, one could not determine whether vessel occlusion or abnormal narrowing is the cause of an infarct.
Longitudinal change in the neural bases of adolescent social self-evaluations: effects of age and pubertal development.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013

Self-evaluations undergo significant transformation during early adolescence, developing in parallel with the heightened complexity of teenagers' social worlds. Intuitive theories of adolescent development, based in part on animal work, suggest that puberty is associated with neural-level changes that facilitate a "social reorientation" (Nelson et al., 2005). However, direct tests of this hypothesis using neuroimaging are limited in humans. This longitudinal fMRI study examined neurodevelopmental trajectories associated with puberty, self-evaluations, and the presumed social reorientation during the transition from childhood to adolescence. Participants (N = 27, mean age = 10.1 and 13.1 years at time points one and two, respectively) engaged in trait evaluations of two targets (the self and a familiar fictional other), across two domains of competence (social and academic). Responses in ventromedial PFC increased with both age and pubertal development during self-evaluations in the social domain, but not in the academic domain. These results suggest that changes in social self-evaluations are intimately connected with biology, not just peer contexts, and provide important empirical support for the relationship between neurodevelopment, puberty, and social functioning.
Expression of suppressor of cytokine signaling genes in human elderly and Alzheimer's disease brains and human microglia.
Neuroscience, 2015

Multiple cellular systems exist to prevent uncontrolled inflammation in brain tissues; the suppressor of cytokine signaling (SOCS) proteins have key roles in these processes. SOCS proteins are involved in restricting cellular signaling pathways by enhancing the degradation of activated receptors and removing the stimuli for continued activation. There are eight separate SOCS genes that code for proteins with similar structures and properties. All SOCS proteins can reduce signaling of activated transcription factors Janus kinase (JAK) and signal transducer and activator of transcription (STAT), but they also regulate many other signaling pathways. SOCS-1 and SOCS-3 have particular roles in regulating inflammatory processes. Chronic inflammation is a key feature of the pathology present in Alzheimer's disease (AD)-affected brains resulting from responses to amyloid plaques or neurofibrillary tangles, the pathological hallmarks of AD. The goal of this study was to examine SOCS gene expression in human non-demented (ND) and AD brains and in human brain-derived microglia to determine if AD-related pathology resulted in a deficit of these critical molecules. We demonstrated that SOCS-1, SOCS-2, SOCS-3 and cytokine-inducible SH2 containing protein (CIS) mRNA expression was increased in amyloid beta peptide (Aβ)- and inflammatory-stimulated microglia, while SOCS-6 mRNA expression was decreased by both types of treatments. Using human brain samples from the temporal cortex from ND and AD cases, SOCS-1 through SOCS-7 and CIS mRNA and SOCS-1 through SOCS-7 protein could be detected constitutively in ND and AD human brain samples. Although, the expression of key SOCS genes did not change to a large extent as a result of AD pathology, there were significantly increased levels of SOCS-2, SOCS-3 and CIS mRNA and increased protein levels of SOCS-4 and SOCS-7 in AD brains. In summary, there was no evidence of a deficit of these key inflammatory regulating proteins in aged or AD brains.
Musculoskeletal Ultrasound in the Emergency Department.
Seminars in musculoskeletal radiology, 2020

The skin, nerves, and tendons are superficial anatomical structures that can easily be investigated with an ultrasound (US) examination in the emergency department (ED). US evaluation is relatively underused in musculoskeletal evaluation when compared with other emergency applications, such as abdominal trauma, possible aortic aneurysm, and in the cardiovascular system. The aim of this article is to revise the main bone and soft tissue conditions that can be assessed using US in the ED.
Basal ganglia reign through downstream control of motor centers in midbrain and brain stem while updating cortex with efference copy information.
Neuron, 2021

In this issue of Neuron, McElvain et al. (2021) show that the major output of the basal ganglia, the substantia nigra pars reticulata, targets no fewer than 42 midbrain and brainstem structures and conveys an efference copy of the downstream commands back via thalamus to the cortex and striatum.
Electron paramagnetic resonance microscopy using spins in diamond under ambient conditions.
Nature communications, 2017

Magnetic resonance spectroscopy is one of the most important tools in chemical and bio-medical research. However, sensitivity limitations typically restrict imaging resolution to ~ 10 µm. Here we bring quantum control to the detection of chemical systems to demonstrate high-resolution electron spin imaging using the quantum properties of an array of nitrogen-vacancy centres in diamond. Our electron paramagnetic resonance microscope selectively images electronic spin species by precisely tuning a magnetic field to bring the quantum probes into resonance with the external target spins. This provides diffraction limited spatial resolution of the target spin species over a field of view of 50 × 50 µm
Astrocytes in heavy metal neurotoxicity and neurodegeneration.
Brain research, 2021

With the industrial development and progressive increase in environmental pollution, the mankind overexposure to heavy metals emerges as a pressing public health issue. Excessive intake of heavy metals, such as arsenic (As), manganese (Mn), mercury (Hg), aluminium (Al), lead (Pb), nickel (Ni), bismuth (Bi), cadmium (Cd), copper (Cu), zinc (Zn), and iron (Fe), is neurotoxic and it promotes neurodegeneration. Astrocytes are primary homeostatic cells in the central nervous system. They protect neurons against all types of insults, in particular by accumulating heavy metals. However, this makes astrocytes the main target for heavy metals neurotoxicity. Intake of heavy metals affects astroglial homeostatic and neuroprotective cascades including glutamate/GABA-glutamine shuttle, antioxidative machinery and energy metabolism. Deficits in these astroglial pathways facilitate or even instigate neurodegeneration. In this review, we provide a concise outlook on heavy metal-induced astrogliopathies and their association with major neurodegenerative disorders. In particular, we focus on astroglial mechanisms of iron-induced neurotoxicity. Iron deposits in the brain are detected in main neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis. Accumulation of iron in the brain is associated with motor and cognitive impairments and iron-induced histopathological manifestations may be considered as the potential diagnostic biomarker of neurodegenerative diseases. Effective management of heavy metal neurotoxicity can be regarded as a potential strategy to prevent or retard neurodegenerative pathologies.
A Magnetic Microbead Occlusion Model to Induce Ocular Hypertension-Dependent Glaucoma in Mice.
Journal of visualized experiments : JoVE, 2016

The use of rodent models of glaucoma has been essential to understand the molecular mechanisms that underlie the pathophysiology of this multifactorial neurodegenerative disease. With the advent of numerous transgenic mouse lines, there is increasing interest in inducible murine models of ocular hypertension. Here, we present an occlusion model of glaucoma based on the injection of magnetic microbeads into the anterior chamber of the eye using a modified microneedle with a facetted bevel. The magnetic microbeads are attracted to the iridocorneal angle using a handheld magnet to block the drainage of aqueous humour from the anterior chamber. This disruption in aqueous dynamics results in a steady elevation of intraocular pressure, which subsequently leads to the loss of retinal ganglion cells, as observed in human glaucoma patients. The microbead occlusion model presented in this manuscript is simple compared to other inducible models of glaucoma and also highly effective and reproducible. Importantly, the modifications presented here minimize common issues that often arise in occlusion models. First, the use of a bevelled glass microneedle prevents backflow of microbeads and ensures that minimal damage occurs to the cornea during the injection, thus reducing injury-related effects. Second, the use of magnetic microbeads ensures the ability to attract most beads to the iridocorneal angle, effectively reducing the number of beads floating in the anterior chamber avoiding contact with other structures (e.g., iris, lens). Lastly, the use of a handheld magnet allows flexibility when handling the small mouse eye to efficiently direct the magnetic microbeads and ensure that there is little reflux of the microbeads from the eye when the microneedle is withdrawn. In summary, the microbead occlusion mouse model presented here is a powerful investigative tool to study neurodegenerative changes that occur during the onset and progression of glaucoma.
Dietary Emulsifiers Directly Impact Adherent-Invasive E. coli Gene Expression to Drive Chronic Intestinal Inflammation.
Cell reports, 2020

Dietary emulsifiers carboxymethylcellulose (CMC) and polysorbate-80 (P80) disturb gut microbiota, promoting chronic inflammation. Mice with minimal microbiota are protected against emulsifiers' effects, leading us to hypothesize that these compounds might provoke select pathobionts to promote inflammation. Gnotobiotic wild-type (WT) and interleukin-10 (IL-10)
Ca
Journal of chemical neuroanatomy, 2017

The antidepressant-sensitive norepinephrine (NE) transporter (NET) inactivates NE released during central and peripheral neuronal activity by transport into presynaptic cells. Altered NE clearance due to dysfunction of NET has been associated with the development of mental illness and cardiovascular diseases. NET activity in vivo is influenced by stress, neuronal activity, hormones and drugs. We investigated the mechanisms of Ca
When perceptions defy reality: The relationships between depression and actual and perceived Facebook social support.
Journal of affective disorders, 2016

Although the relationship between depression and "offline" social support is well established, numerous questions surround the relationship between "online" social support and depression. We explored this issue by examining the social support dynamics that characterize the way individuals with varying levels of depression (Study 1) and SCID-diagnosed clinically depressed and non-depressed individuals (Study 2) interact with Facebook, the world's largest online social network.
Astroglial-axonal interactions during early stages of myelination in mixed cultures using in vitro and ex vivo imaging techniques.
BMC neuroscience, 2014

[corrected] Myelination is a very complex process that requires the cross talk between various neural cell types. Previously, using cytosolic or membrane associated GFP tagged neurospheres, we followed the interaction of oligodendrocytes with axons using time-lapse imaging in vitro and ex vivo and demonstrated dynamic changes in cell morphology. In this study we focus on GFP tagged astrocytes differentiated from neurospheres and their interactions with axons.
The enigmatic mossy cell of the dentate gyrus.
Nature reviews. Neuroscience, 2016

Mossy cells comprise a large fraction of the cells in the hippocampal dentate gyrus, suggesting that their function in this region is important. They are vulnerable to ischaemia, traumatic brain injury and seizures, and their loss could contribute to dentate gyrus dysfunction in such conditions. Mossy cell function has been unclear because these cells innervate both glutamatergic and GABAergic neurons within the dentate gyrus, contributing to a complex circuitry. It has also been difficult to directly and selectively manipulate mossy cells to study their function. In light of the new data generated using methods to preferentially eliminate or activate mossy cells in mice, it is timely to ask whether mossy cells have become any less enigmatic than they were in the past.
Service Use Following First-Episode Schizophrenia Among Commercially Insured Youth.
Schizophrenia bulletin, 2020

To investigate patterns of mental health service and antipsychotic use following a first-episode schizophrenia (FES) and to examine the role of the treatment setting in which individuals are first diagnosed.
Cerebral blood flow and gray matter volume covariance patterns of cognition in aging.
Human brain mapping, 2013

Advancing age results in altered cognitive and neuroimaging-derived markers of neural integrity. Whether cognitive changes are the result of variations in brain measures remains unclear and relating the two across the lifespan poses a unique set of problems. It must be determined whether statistical associations between cognitive and brain measures truly exist and are not epiphenomenal due solely to their shared relationships with age. The purpose of this study was to determine whether cerebral blood flow (CBF) and gray matter volume (GMV) measures make unique and better predictions of cognition than age alone. Multivariate analyses identified brain-wide covariance patterns from 35 healthy young and 23 healthy older adults using MRI-derived measures of CBF and GMV related to three cognitive composite scores (i.e., memory, fluid ability, and speed/attention). These brain-cognitive relationships were consistent across the age range, and not the result of epiphenomenal associations with age and each imaging modality provided its own unique information. The CBF and GMV patterns each accounted for unique aspects of cognition and accounted for nearly all the age-related variance in the cognitive composite scores. The findings suggest that measures derived from multiple imaging modalities explain larger amounts of variance in cognition providing a more complete understanding of the aging brain.
Treatment with gut bifidobacteria improves hippocampal plasticity and cognitive behavior in adult healthy rats.
Neuropharmacology, 2020

At the present time, gut microbiota inspires great interest in the field of neuroscience as a function of its role in normal physiology and involvement in brain function. This aspect suggests a specific gut-brain pathway, mainly modulated by gut microbiota activity. Among the multiple actions controlled by microbiota at the brain level, neuronal plasticity and cognitive function represent two of the most interesting aspects of this cross-talk communication. We address the possible action of two-months implementation of gut Bifidobacteria using a mixture of three different strains (B-MIX) on hippocampal plasticity and related cognitive behavior in adult healthy Sprague Dawley rats. B-MIX treatment increases the hippocampal BDNF with a parallel gain in dendritic spines' density of hippocampal CA1 pyramidal neurons. Electrophysiological experiments revealed a significant increment of HFS-induced LTP formation on the CA1 hippocampal region in B-MIX treated rats. All these effects are accompanied by a better cognitive performance observed in B-MIX treated animals with no impairments in locomotion activity. Therefore, in adult rats, the treatment with different strains of bifidobacteria is able to markedly enhance neuronal plasticity and the CNS function influencing cognitive behavior, an effect that may suggest a potential therapeutic treatment in brain diseases associated with cognitive functions.
Prevalence and incidence of sarcopenia in the very old: findings from the Newcastle 85+ Study.
Journal of cachexia, sarcopenia and muscle, 2017

Recognition that an older person has sarcopenia is important because this condition is linked to a range of adverse outcomes. Sarcopenia becomes increasingly common with age, and yet there are few data concerning its descriptive epidemiology in the very old (aged 85 years and above). Our aims were to describe risk factors for sarcopenia and estimate its prevalence and incidence in a British sample of the very old.
Schizophrenia and depression, two poles of endocannabinoid system deregulation.
Translational psychiatry, 2017

The activity of certain G protein-coupled receptors (GPCRs) and of glutamate N-Methyl-D-aspartate receptors (NMDARs) is altered in both schizophrenia and depression. Using postmortem prefrontal cortex samples from subjects with schizophrenia or depression, we observed a series of opposite changes in the expression of signaling proteins that have been implicated in the cross-talk between GPCRs and NMDARs. Thus, the levels of HINT1 proteins and NMDAR NR1 subunits carrying the C1 cytosolic segment were increased in depressives and decreased in schizophrenics, respect to matched controls. The differences in NR1 C1 subunits were compensated for via altered expression of NR1 subunits lacking the C1 segment; thus, the total number of NR1 subunits was comparable among the three groups. GPCRs influence the function of NR1 C1-containing NMDARs via PKC/Src, and thus, the association of mu-opioid and dopamine 2 receptors with NR1 C1 subunits was augmented in depressives and decreased in schizophrenics. However, the association of cannabinoid 1 receptors (CB1Rs) with NR1 C1 remained nearly constant. Endocannabinoids, via CB1Rs, control the presence of NR1 C1 subunits in the neural membrane. Thus, an altered endocannabinoid system may contribute to the pathophysiology of schizophrenia and depression by modifying the HINT1-NR1 C1/GPCR ratio, thereby altering GPCR-NMDAR cross-regulation.