rudyvdbrink/CitationDatabase huggingface dataset:
Attenuation of proliferation in oligodendrocyte precursor cells by activated microglia.
Journal of neuroscience research, 2010

Activated microglia can influence the survival of neural cells through the release of cytotoxic factors. Here, we investigated the interaction between Toll-like receptor 4 (TLR4)-activated microglia and oligodendrocytes or their precursor cells (OPC). Primary rat or N9 microglial cells were activated by exposure to TLR4-specifc lipopolysaccharide (LPS), resulting in mitogen-activated protein kinase activation, increased CD68 and inducible nitric oxide synthase expression, and release of the proinflammatory cytokines tumor necrosis factor (TNF) and interleukin-6 (IL-6). Microglial conditioned medium (MGCM) from LPS-activated microglia attenuated primary OPC proliferation without inducing cell death. The microglial-induced inhibition of OPC proliferation was reversed by stimulating group III metabotropic glutamate receptors in microglia with the agonist L-AP4. In contrast to OPC, LPS-activated MGCM enhanced the survival of mature oligodendrocytes. Further investigation suggested that TNF and IL-6 released from TLR4-activated microglia might contribute to the effect of MGCM on OPC proliferation, insofar as TNF depletion of LPS-activated MGCM reduced the inhibition of OPC proliferation, and direct addition of TNF or IL-6 attenuated or increased proliferation, respectively. OPC themselves were also found to express proteins involved in TLR4 signalling, including TLR4, MyD88, and MAL. Although LPS stimulation of OPC did not induce proinflammatory cytokine release or affect their survival, it did trigger JNK phosphorylation, suggesting that TLR4 signalling in these cells is active. These findings suggest that OPC survival may be influenced not only by factors released from endotoxin-activated microglia but also through a direct response to endotoxins. This may have consequences for myelination under conditions in which microglial activation and cerebral infection are both implicated. , Inc.
Cholesterol reduction impairs exocytosis of synaptic vesicles.
Journal of cell science, 2010

Cholesterol and sphingolipids are abundant in neuronal membranes, where they help the organisation of the membrane microdomains involved in major roles such as axonal and dendritic growth, and synapse and spine stability. The aim of this study was to analyse their roles in presynaptic physiology. We first confirmed the presence of proteins of the exocytic machinery (SNARES and Ca(v)2.1 channels) in the lipid microdomains of cultured neurons, and then incubated the neurons with fumonisin B (an inhibitor of sphingolipid synthesis), or with mevastatin or zaragozic acid (two compounds that affect the synthesis of cholesterol by inhibiting HMG-CoA reductase or squalene synthase). The results demonstrate that fumonisin B and zaragozic acid efficiently decrease sphingolipid and cholesterol levels without greatly affecting the viability of neurons or the expression of synaptic proteins. Electron microscopy showed that the morphology and number of synaptic vesicles in the presynaptic boutons of cholesterol-depleted neurons were similar to those observed in control neurons. Zaragozic acid (but not fumonisin B) treatment impaired synaptic vesicle uptake of the lipophilic dye FM1-43 and an antibody directed against the luminal epitope of synaptotagmin-1, effects that depended on the reduction in cholesterol because they were reversed by cholesterol reloading. The time-lapse confocal imaging of neurons transfected with ecliptic SynaptopHluorin showed that cholesterol depletion affects the post-depolarisation increase in fluorescence intensity. Taken together, these findings show that reduced cholesterol levels impair synaptic vesicle exocytosis in cultured neurons.
Effects of storytelling on the childhood brain: near-infrared spectroscopic comparison with the effects of picture-book reading.
Fukushima journal of medical science, 2018

In children, storytelling provides many psychological and educational benefits, such as enhanced imagination to help visualize spoken words, improved vocabulary, and more refined communication skills. However, the brain mechanisms underlying the effects of storytelling on children are not clear. In this study, the effects of storytelling on the brains of children were assessed by using near-infrared spectroscopy (NIRS). Results indicated significant decreases of the blood flow in the bilateral prefrontal areas during picture-book reading when the subjects were familiarized in comparison to the cases of the subject naïve to the stories. However, no significant differences in the blood flow were found during storytelling between the subjects naïve and familiarized to the stories. The results indicated more sustained brain activation to storytelling in comparison with picture-book reading, suggesting possible advantages of storytelling as a psychological and educational medium in children.
Multimodal MR imaging of brain iron in attention deficit hyperactivity disorder: a noninvasive biomarker that responds to psychostimulant treatment?
Radiology, 2014

To comprehensively assess brain iron levels in typically developing control subjects and patients with attention deficit hyperactivity disorder (ADHD) when psychostimulant medication history is accounted for.
Use of paracetamol during pregnancy and child neurological development.
Developmental medicine and child neurology, 2015

Paracetamol (acetaminophen) remains the first line for the treatment of pain and fever in pregnancy. Recently published epidemiological studies suggested a possible association between paracetamol exposure in utero and attention-deficit-hyperactivity disorder/hyperkinetic disorder (ADHD/HKD) or adverse development issues in children. However, the effects observed are in the weak to moderate range, and limitations in the studies' design prevent inference on a causal association with ADHD/HKD or child neurological development. In parallel, recent animal data showed that cognition and behaviour may be altered following exposure to therapeutic doses of paracetamol during early development. These effects may be mediated by interference of paracetamol with brain-derived neurotrophic factor, neurotransmitter systems (including serotonergic, dopaminergic, adrenergic, as well as the endogenous endocannabinoid systems), or cyclooxygenase-2. However, no firm conclusion can be made on the relevance of these observations to humans. We conclude that additional well-designed cohort studies are necessary to confirm or disprove the association. In the context of current knowledge, paracetamol is still to be considered safe in pregnancy and should remain the first-line treatment for pain and fever.
Real-time in vivo imaging reveals the ability of monocytes to clear vascular amyloid beta.
Cell reports, 2013

Alzheimer's disease (AD) is characterized by the accumulation of amyloid beta (Aβ) that is assumed to result from impaired elimination of this neurotoxic peptide. Most patients with AD also exhibit cerebral amyloid angiopathy, which consists of Aβ deposition within the cerebral vasculature. The contribution of monocytes in AD has so far been limited to macrophage precursors. In this study, we aimed to investigate whether circulating monocytes could play a role in the elimination of Aβ. With live intravital two-photon microscopy, we demonstrate that patrolling monocytes are attracted to and crawl onto the luminal walls of Aβ-positive veins, but not on Aβ-positive arteries or Aβ-free blood vessels. Additionally, we report the presence of crawling monocytes carrying Aβ in veins and their ability to circulate back into the bloodstream. Selective removal of Ly6C(lo) monocytes in APP/PS1 mice induced a significant increase of Aβ load in the cortex and hippocampus. These data uncover the ability of Ly6C(lo) monocytes to naturally target and eliminate Aβ within the lumen of veins and constitute a potential therapeutic target in AD.
Preserving the balance: diverse forms of long-term GABAergic synaptic plasticity.
Nature reviews. Neuroscience, 2019

Cellular mechanisms that regulate the interplay of synaptic excitation and inhibition are thought to be central to the functional stability of healthy neuronal circuits. A growing body of literature demonstrates the capacity for inhibitory GABAergic synapses to exhibit long-term plasticity in response to changes in neuronal activity. Here, we review this expanding field of research, focusing on the diversity of mechanisms that link glutamatergic signalling, postsynaptic action potentials and inhibitory synaptic strength. Several lines of evidence indicate that multiple, parallel forms of plasticity serve to regulate activity at both the input and output domains of individual neurons. Overall, these varied phenomena serve to promote both stability and flexibility over the life of the organism.
The Persistence of Experience: Prior Attentional and Emotional State Affects Network Functioning in a Target Detection Task.
Cerebral cortex (New York, N.Y. : 1991), 2015

Efficient, adaptive behavior relies on the ability to flexibly move between internally focused (IF) and externally focused (EF) attentional states. Despite evidence that IF cognitive processes such as event imagination comprise a significant amount of awake cognition, the consequences of internal absorption on the subsequent recruitment of brain networks during EF tasks are unknown. The present functional magnetic resonance imaging (fMRI) study employed a novel attentional state switching task. Subjects imagined positive and negative events (IF task) or performed a working memory task (EF task) before switching to a target detection (TD) task also requiring attention to external information, allowing for the investigation of neural functioning during external attention based on prior attentional state. There was a robust increase of activity in frontal, parietal, and temporal regions during TD when subjects were previously performing the EF compared with IF task, an effect that was most pronounced following negative IF. Additionally, dorsolateral prefrontal cortex was less negatively coupled with ventromedial prefrontal and posterior cingulate cortices during TD following IF compared with EF. These findings reveal the striking consequences for brain activity following immersion in an IF attentional state, which have strong implications for psychiatric disorders characterized by excessive internal focus.
To PFKFB3 or Not to PFKFB3, That Is the Question.
Cancer cell, 2016

In this issue of Cancer Cell, Cantelmo et al. describe how reduction of PFKFB3 enzyme activity can promote vascular normalization. The authors show in turn how this affects vascular permeability and can ultimately improve the efficacy of chemotherapeutic agents.
Optogenetic dissection of neural circuitry: from synaptic causalities to blue prints for novel treatments of behavioral diseases.
Current opinion in neurobiology, 2015

Optogenetics has enabled the characterization of the neural circuits involved in brain diseases, such as addiction, depression or obsessive compulsive disorders. Recently, the technique has also been used to propose blueprints for novel treatments aiming at restoring circuit function through the reversal of specific forms of synaptic plasticity. Since optogenetic manipulations cannot be immediately translated to human use, we argue that an intermediate strategy could consist of emulating optogenetic protocols with deep brain stimulation (DBS). This translational path to rational, optogenetically inspired DBS protocols starts by refining existing approaches and carries the hope to expand to novel indications.
Non-cell-autonomous actions of α-synuclein: Implications in glial synucleinopathies.
Progress in neurobiology, 2018

Many neurodegenerative diseases are derived from the combined consequences of genetic and environmental factors. One of the common features implicated in the neurodegenerative processes is aggregation of disease-specific neuronal proteins. These proteins are accumulated not only directly in neurons, but also indirectly involve glial cells. Whereas the focus of research has been directed towards the impacts of protein aggregation upon neurons, the influence that it exerts on glial cells has been relatively overlooked. Recent studies, however, provide strong evidence on pathogenic responses of glial cells originated from the neuron-derived protein aggregates. Here, we critically examine the latest advancement in investigating how glial cells are activated in neurodegenerative disorders that are associated with α-synuclein aggregates. Often referred to as synucleinopathies, these include Parkinson disease, dementia with Lewy bodies, and multiple system atrophy. To further illustrate, we would discuss paracrine actions of α-synuclein aggregates secreted from neuronal cells in promoting pathogenic reactions from various types of glia and evaluate the non-cell-autonomous mechanism compared to a cell-autonomous one. Such analyses of the impacts of glial responses in neurodegenerative diseases, in the long term, could be further utilized in developing different treatments of the diseases and potentially discovering new drugs.
Biased allosteric agonism and modulation of metabotropic glutamate receptor 5: Implications for optimizing preclinical neuroscience drug discovery.
Neuropharmacology, 2017

Allosteric modulators, that exhibit no intrinsic agonist activity, offer the advantage of spatial and temporal fine-tuning of endogenous agonist activity, allowing the potential for increased selectivity, reduced adverse effects and improved clinical outcomes. Some allosteric ligands can differentially activate and/or modulate distinct signaling pathways arising from the same receptor, phenomena referred to as 'biased agonism' and 'biased modulation'. Emerging evidence for CNS disorders with glutamatergic dysfunction suggests the metabotropic glutamate receptor subtype 5 (mGlu
Applying neuroimaging to detect neuroanatomical dysconnectivity in psychosis.
Epidemiology and psychiatric sciences, 2015

This editorial discusses the application of a novel brain imaging analysis technique in the assessment of neuroanatomical dysconnectivity in psychotic illnesses. There has long been a clinical interest in psychosis as a disconnection syndrome. In recent years graph theory metrics have been applied to functional and structural imaging datasets to derive measures of brain connectivity, which represent the efficiency of brain networks. These metrics can be derived from structural neuroimaging datasets acquired using diffusion imaging whereby cortical structures are parcellated into nodes and white matter tracts represent edges connecting these nodes. Furthermore neuroanatomical measures of connectivity may be decoupled from measures of physiological connectivity as assessed using functional imaging, underpinning the need for multi-modal imaging approaches to probe brain networks. Studies to date have reported a number of structural brain connectivity abnormalities associated with schizophrenia that carry potential as illness biomarkers. Structural connectivity abnormalities have also been reported in well patients with bipolar disorder and in unaffected relatives of patients with schizophrenia. Such connectivity metrics may represent clinically relevant biomarkers in studies employing a longitudinal design of illness course in psychosis.
Understanding disease progression and improving Alzheimer's disease clinical trials: Recent highlights from the Alzheimer's Disease Neuroimaging Initiative.
Alzheimer's & dementia : the journal of the Alzheimer's Association, 2019

The overall goal of the Alzheimer's Disease Neuroimaging Initiative (ADNI) is to validate biomarkers for Alzheimer's disease (AD) clinical trials. ADNI is a multisite, longitudinal, observational study that has collected many biomarkers since 2004. Recent publications highlight the multifactorial nature of late-onset AD. We discuss selected topics that provide insights into AD progression and outline how this knowledge may improve clinical trials.
Genetic analysis of CHCHD2 gene in Chinese Parkinson's disease.
American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics, 2016

Recently, mutations in the coiled-coil-helix-coiled-coil-helix domain containing 2 (CHCHD2) gene have been identified in Japanese families with autosomal dominant Parkinson's disease (PD) and two single nucleotide variants (rs10043 and Pro2Leu) increased risk of sporadic PD. The role of CHCHD2 in PD susceptibility in other Asian populations still remains to be clarified. In a large Chinese cohort from mainland China (31 familial PD patients, 1,027 sporadic PD patients, and 1,095 health controls), we examined the association of rs10043 and Pro2Leu variants in CHCHD2 with PD. All subjects were homozygous for rs10043. Moreover, we detected six patients (0.57%, one of the six patients has family history) and three controls (0.27%) with a heterozygous Pro2Leu variant. Though the frequency of Pro2Leu variant was two times higher in PD compared to controls, the difference did not reach significance in genotypic distribution (P = 0.47) or allelic distribution (P = 0.47). However, our meta-analysis in Asian populations revealed that the frequency of Pro2Leu variant was significantly higher in PD patients than in controls (P = 0.0002). Our study suggests that Pro2Leu in CHCHD2 may be a risk factor for PD among Asians. © 2016 Wiley Periodicals, Inc.
Sensory experience modifies feature map relationships in visual cortex.
eLife, 2016

The extent to which brain structure is influenced by sensory input during development is a critical but controversial question. A paradigmatic system for studying this is the mammalian visual cortex. Maps of orientation preference (OP) and ocular dominance (OD) in the primary visual cortex of ferrets, cats and monkeys can be individually changed by altered visual input. However, the spatial relationship between OP and OD maps has appeared immutable. Using a computational model we predicted that biasing the visual input to orthogonal orientation in the two eyes should cause a shift of OP pinwheels towards the border of OD columns. We then confirmed this prediction by rearing cats wearing orthogonally oriented cylindrical lenses over each eye. Thus, the spatial relationship between OP and OD maps can be modified by visual experience, revealing a previously unknown degree of brain plasticity in response to sensory input.
Adult neurogenesis and the dentate gyrus: Predicting function from form.
Behavioural brain research, 2020

Hypotheses about the functional properties of the dentate gyrus and adult dentate neurogenesis have been shaped by early observations of the anatomy of this region, mostly in rodents. This has led to the development of a few core propositions that have guided research over the past several years, including the predicted role of this region in pattern separation and the local transformation of inputs from the entorhinal cortex. We now have the opportunity to review these predictions and update these anatomical observations based on recently developed techniques that reveal the complex structure, connectivity, and dynamic properties of distinct cell populations in the dentate gyrus at a higher resolution. Cumulative evidence suggests that the dentate gyrus and adult-born granule cells play a role in some forms of behavioral discriminations, but there are still many unanswered questions about how the dentate gyrus processes information to support the disambiguation of stimuli.
Association between worldwide dietary and lifestyle patterns with total cholesterol concentrations and DALYs for infectious and cardiovascular diseases: an ecological analysis.
Journal of epidemiology and global health, 2015

Global dietary and lifestyle trends are primary risk factors for communicable and non-communicable diseases. An ecological analysis was conducted to examine the association of global dietary and lifestyle patterns with total cholesterol concentrations. This study also investigated whether total cholesterol modified the association between dietary and lifestyle habits with disability-adjusted-life-years-lost (DALYs) for infectious and cardiovascular diseases (CVDs). Country-specific mean total cholesterol concentrations and DALYs for infectious and CVDs were obtained. Data were then matched to country-specific food and energy availability for consumption and information on obesity, physical inactivity, urbanization, gross domestic product (GDP), life expectancy and smoking. Stepwise multiple regression models were developed to identify significant predictors of total cholesterol concentrations and DALYs for infectious and CVDs. Life expectancy and egg and meat consumption were significantly associated with cholesterol concentrations. DALYs for infectious diseases were associated with smoking, life expectancy and per capita GDP. Smoking was the only predictor of DALYs for CVDs. The improvement of socio-demographic conditions and economic growth is likely to reduce the burden of communicable diseases in developing countries. A concurring increase in non-communicable diseases is expected, and these results have, yet again, identified smoking as a primary risk factor for CVDs.
Localised Collagen2a1 secretion supports lymphatic endothelial cell migration in the zebrafish embryo.
Development (Cambridge, England), 2020

The lymphatic vasculature develops primarily from pre-existing veins. A pool of lymphatic endothelial cells (LECs) first sprouts from cardinal veins followed by migration and proliferation to colonise embryonic tissues. Although much is known about the molecular regulation of LEC fate and sprouting during early lymphangiogenesis, we know far less about the instructive and permissive signals that support LEC migration through the embryo. Using a forward genetic screen, we identified
Postural Adjustments during Interactions with an Active Partner.
Neuroscience, 2021

Ensuring stability of the human vertical posture is a complex task requiring both anticipatory and compensatory postural strategies when a standing person performs fast actions and interacts with the environment, which can include other persons. How people adjust their preparatory and compensatory postural adjustments in situations when they interact with an active partner is still poorly understood. In this study we investigated the postural adjustments while two healthy persons played a traditional childhood game. While standing facing each other, they were asked to push with their hands against the hands of the opponent only, and to make the opponent to take a step. We explored strategies when pushing the opponent's hands generated perturbations to the posture of both players and when one of the players withdrew the arms to neutralize the opponent's pushing action. Electromyograms were recorded from the leg and trunk muscles and used to quantify early (EPAs), anticipatory (APAs) and compensatory (CPAs) postural adjustments, as well as the co-activation and reciprocal changes in the activity of agonist-antagonist pairs. Results showed higher indices of muscle co-activation during EPAs during the game compared to the control conditions. We found that postural preparation strategies defined whether a participant kept or lost balance during the game. Our results highlight the importance of muscle co-activation, the role of anticipation, and the difference in strategies while interacting with an active partner as compared to interactions with passive objects.