rudyvdbrink/CitationDatabase huggingface dataset:
High hopes for CB(2) receptors in neurogenesis.
British journal of pharmacology, 2014

During life, new neurons are continually added to hippocampal circuitry, with evidence suggesting that these adult-born neurons are functionally linked to cognition and emotion. The mammalian brain contains actively dividing neural stem cells in discrete regions, including the subventricular zone of the lateral ventricles and the subgranular zone of the dentate gyrus. Once mature, these neurons integrate into neuronal networks, forming synaptic connections with interneurons, mossy cells and CA3 pyramidal cells
Sequential formation of different layers of dystrophic neurites in Alzheimer's brains.
Molecular psychiatry, 2019

Alzheimer's disease (AD) is characterized by the presence of neuritic plaques in which dystrophic neurites (DNs) are typical constituents. We recently showed that DNs labeled by antibodies to the tubular endoplasmic reticulum (ER) protein reticulon-3 (RTN3) are enriched with clustered tubular ER. However, multi-vesicle bodies are also found in DNs, suggesting that different populations of DNs exist in brains of AD patients. To understand how different DNs evolve to surround core amyloid plaques, we monitored the growth of DNs in AD mouse brains (5xFAD and APP/PS1ΔE9 mice) by multiple approaches, including two-dimensional and three-dimensional (3D) electron microscopy (EM). We discovered that a pre-autophagosome protein ATG9A was enriched in DNs when a plaque was just beginning to develop. ATG9A-positive DNs were often closer to the core amyloid plaque, whereas RTN3 immunoreactive DNs were mostly located in the outer layers of ATG9A-positive DNs. Proteins such as RAB7 and LC3 appeared in DNs at later stages during plaque growth, likely accumulated as a part of large autophagy vesicles, and were distributed relatively furthest from the core amyloid plaque. Reconstructing the 3D structure of different morphologies of DNs revealed that DNs in AD mouse brains were constituted in three layers that are distinct by enriching different types of vesicles, as validated by immune-EM methods. Collectively, our results provide the first evidence that DNs evolve from dysfunctions of pre-autophagosomes, tubular ER, mature autophagosomes, and the ubiquitin proteasome system during plaque growth.
A Naturally Occurring Polymorphism in the HIV-1 Tat Basic Domain Inhibits Uptake by Bystander Cells and Leads to Reduced Neuroinflammation.
Scientific reports, 2019

HIV-1 Tat protein contributes to HIV-neuropathogenesis in several ways including its ability to be taken up by uninfected bystander CNS cells and to activate inflammatory host genes causing synaptic injury. Here, we report that in the globally dominant HIV-1 clade C, Tat displays a naturally occurring polymorphism, R57S, in its basic domain, which mediates cellular uptake. We examined the effect of this polymorphism on Tat uptake and its consequences for cellular gene transactivation. In decapeptides corresponding to the basic domain, a R57S substitution caused up to a 70% reduction in uptake. We also used a transcellular Tat transactivation assay, where we expressed Tat proteins of HIV-1 clade B (Tat-B) or C (Tat-C) or their position 57 variants in HeLa cells. We quantified the secreted Tat proteins and measured their uptake by TZM-bl cells, which provide readout via an HIV-1 Tat-responsive luciferase gene. Transactivation by Tat-B was significantly reduced by R57S substitution, while that of Tat-C was enhanced by the reciprocal S57R substitution. Finally, we exposed microglia to Tat variants and found that R57 is required for maximal neuroinflammation. The R57S substitution dampened this response. Thus, genetic variations can modulate the ability of HIV-1 Tat to systemically disseminate neuroinflammation.
Intrinsic connectivity networks and personality: the temperament dimension harm avoidance moderates functional connectivity in the resting brain.
Neuroscience, 2013

Recent functional imaging studies that examined functional connectivity in the resting brain have demonstrated various intrinsic connectivity networks (ICNs). Certain patterns of over- and underactivity in various ICNs have been hypothesized to form the neural basis of psychiatric disorders. Furthermore, activity in the ICNs does not reflect ongoing mental activity but the maintenance of neural circuits in a ready state suggesting not only relationships between ICNs and disorders but also correlations between ICNs and personality. In the present study, we assess the relationship between trait anxiety, a well established endophenotype of anxiety disorders, and functional connectivities within the insular salience ICN in a sample of healthy female subjects. Based on a previous study that demonstrated the functional relevance of the insular salience ICN for state anxiety, we used the harm avoidance scale from the Temperament and Character Inventory (TCI) as a trait marker to demonstrate increased functional connectivity within the insular salience ICN. Specifically, the functional connectivity between the anterior insula and the anterior cingulate and between the anterior insula and the dorsolateral prefrontal cortex were positively correlated with individual harm avoidance scores. The results fit into previous work, provide evidence for a potential biomarker of anxiety disorders and, most importantly, demonstrate a direct neural correlate of the personality trait harm avoidance in the absence of external stimulation.
Attenuation of auditory ERPs to action-sound coincidences is not explained by voluntary allocation of attention.
Psychophysiology, 2013

The event-related potential (ERP) correlates of sound detection are attenuated when eliciting sounds coincide with our own actions. The role of attention in this effect was investigated in two experiments by presenting tones separated by random intervals. In the homogeneous condition of Experiments 1 and 2, the same tone was repeated, whereas in the mixed condition of Experiment 1, tones with five different frequencies were presented. Participants performed a time-interval production task by marking intervals with keypresses in Experiment 1, and tried to produce keypress-tone coincidences in Experiment 2. Although the auditory ERPs were attenuated for coincidences, no modulation by the multiplicity of tone frequencies in Experiment 1, or by the task-relevancy of tones and coincidences in Experiment 2, was found. This suggests that coincidence-related ERP attenuation cannot be fully explained by voluntary attentional mechanisms.
Predicting anxiety state using smartphone-based passive sensing.
Journal of biomedical informatics, 2019

This study predicts the change of stress levels using real-world and online behavioral features extracted from smartphone log information. Previous studies of stress detection using smartphone data focused on a single feature and did not consider all features simultaneously. We propose a method to extract a co-occurring combination of a user's real-world and online behavioral features by converting raw sensor data into categorical features. We conducted an experiment in which the State Trait Anxiety Inventory (STAI) was used to assess the anxiety-related stress levels of 20 healthy participants. The participants installed a log-collecting application on their smartphones and answered the STAI questions once a day for one month. The proposed method showed an F-score of 74.2%, which is 4.0% higher than the F-score of previous studies (70.2%) that used single non-combined features. The results demonstrate that anxiety-related stress levels can be predicted using combined features extracted from smartphone log data.
Expression of phosphatase and tensin homolog, epidermal growth factor receptor, and Ki-67 in astrocytoma: A prospective study in a tertiary care hospital.
Indian journal of medical and paediatric oncology : official journal of Indian Society of Medical & Paediatric Oncology, 2014

Though the tumor grade is a key factor influencing the choice of therapies, particularly determining the use of adjuvant radiation and specific chemotherapy protocols, role of abnormality in phosphatase and tensin homolog (PTEN) expression and variation in epidermal growth factor receptor (EGFR) labeling index (LI) and Ki-67 LI in survival and clinical outcome have been studied by many researchers in the recent past.
Does task-set reconfiguration create cognitive slack?
Journal of experimental psychology. Human perception and performance, 2005

C. Oriet and P. Jolicoeur (2003) reported 2 experiments in which the perceptual contrast of stimuli was manipulated in a task-switching paradigm. They failed to observe an interaction in the reaction time data between task switching, perceptual contrast, and response-stimulus interval. Using the locus of slack logic, they concluded from these results that early perceptual processing of stimuli awaits the completion of a task-set reconfiguration stage, rather than proceeding in parallel with it. Here, an assumption necessary for this argument is questioned, and it is shown that an existing computational model of task switching, without successive stages for task-set reconfiguration and perceptual processing, produces a similar pattern of data. Thus, C. Oriet and P. Jolicoeur's data are compatible with models in which early perceptual processing and task-set reconfiguration take place in parallel.
Effect of context exposure after fear learning on memory generalization in mice.
Molecular brain, 2016

The conditions under which memory generalization occurs are not well understood. Although it is believed that fear memory generalization is gradually established after learning, it is not clear whether experiences soon after learning affect generalization.
Recommendations for headache service organisation and delivery in Europe.
The journal of headache and pain, 2011

Headache disorders are a major public-health priority, and there is pressing need for effective solutions to them. Better health care for headache-and ready access to it-are central to these solutions; therefore, the organisation of headache-related services within the health systems of Europe becomes an important focus. These recommendations are the result of collaboration between the European Headache Federation and Lifting The Burden: the Global Campaign against Headache. The process of development included wide consultation. To meet the very high level of need for headache care both effectively and efficiently, the recommendations formulate a basic three-level model of health-care organisation rationally spread across primary and secondary health-care sectors, taking account of the different skills and expertise in these sectors. They recognise that health services are differently structured in countries throughout Europe, and not always adequately resourced. Therefore, they aim to be adaptable to suit these differences. They are set out in five sections: needs assessment, description of the model, adaptation, standards and educational implications.
A novel 5HT3 receptor-IGF1 mechanism distinct from SSRI-induced antidepressant effects.
Molecular psychiatry, 2018

Depression is a common mental disorder affecting around 350 million people worldwide. Although selective serotonin reuptake inhibitors (SSRIs) are the most widely used antidepressants, a significant proportion of depressed patients do not achieve remission with SSRIs. In this study, we show that a serotonin type 3 receptor (5HT3R) agonist induces antidepressant effects as well as hippocampal neurogenesis independent of fluoxetine (a commonly used SSRI). Notably, our histological analysis reveals that 5HT3R and insulin-like growth factor 1 (IGF1) are expressed in the same neurons in the subgranular zone of the hippocampal dentate gyrus. Furthermore, our in vivo microdialysis analysis shows that 5HT3R regulates hippocampal extracellular IGF1 levels, and we also show that 5HT3R-dependent hippocampal neurogenesis is mediated by increased IGF1 levels. Altogether, our findings suggest a novel 5HT3R-IGF1 mechanism that is distinct from fluoxetine-induced responses and that provides a new therapeutic target for depression, especially bringing significant benefits for SSRI-resistant depressed patients.
Individual differences in biophysiological toughness: sustaining working memory during physical exhaustion.
Military medicine, 2015

Recent evidence suggests that increased dehydroepiandrosterone sulfate (DHEAS), in combination with decreased cortisol levels have been correlated with enhanced performance outcomes in stressful military environments. This study was implemented to replicate these findings in a group of active duty Air Force members to provide information on the usefulness of these biomarkers indices in the training and operational environment. Seventeen active duty males participated in the 4 sessions of this study. Sessions 1 and 2 were training days for the cognitive testing. Session 3 was a baseline measure of physical fitness, utilizing the VO2 Maximal Treadmill test. Session 4 was centered around a modified-Astrand treadmill protocol designed to induce physical exhaustion. Blood draws for biomarker analysis, cognitive testing (NovaScan), psychomotor vigilance, and physiological measures were collected before, during, and following the treadmill protocol. Results showed that prolonged increases in cortisol negatively correlate with working memory performance. DHEAS release from baseline to poststress was negatively related to the changes in cortisol for 20 minutes following stress. These results indicate that the ratio of DHEAS to cortisol buffers, the effect of cortisol increases that are related to poor working memory performance because of physical exhaustion.
Altered brainstem responses to modafinil in schizophrenia: implications for adjunctive treatment of cognition.
Translational psychiatry, 2018

Candidate pro-cognitive drugs for schizophrenia targeting several neurochemical systems have consistently failed to demonstrate robust efficacy. It remains untested whether concurrent antipsychotic medications exert pharmacodynamic interactions that mitigate pro-cognitive action in patients. We used functional MRI (fMRI) in a randomized, double-blind, placebo-controlled within-subject crossover test of single-dose modafinil effects in 27 medicated schizophrenia patients, interrogating brainstem regions where catecholamine systems arise to innervate the cortex, to link cellular and systems-level models of cognitive control. Modafinil effects were evaluated both within this patient group and compared to a healthy subject group. Modafinil modulated activity in the locus coeruleus (LC) and ventral tegmental area (VTA) in the patient group. However, compared to the healthy comparison group, these effects were altered as a function of task demands: the control-independent drug effect on deactivation was relatively attenuated (shallower) in the LC and exaggerated (deeper) in the VTA; in contrast, again compared to the comparison group, the control-related drug effects on positive activation were attenuated in LC, VTA and the cortical cognitive control network. These altered effects in the LC and VTA were significantly and specifically associated with the degree of antagonism of alpha-2 adrenergic and dopamine-2 receptors, respectively, by concurrently prescribed antipsychotics. These sources of evidence suggest interacting effects on catecholamine neurons of chronic antipsychotic treatment, which respectively increase and decrease sustained neuronal activity in LC and VTA. This is the first direct evidence in a clinical population to suggest that antipsychotic medications alter catecholamine neuronal activity to mitigate pro-cognitive drug action on cortical circuits.
Differential involvement of somatosensory and interoceptive cortices during the observation of affective touch.
Journal of cognitive neuroscience, 2011

Previous studies suggested that the observation of other individuals' somatosensory experiences also activates brain circuits processing one's own somatosensory experiences. However, it is unclear whether cortical regions involved with the elementary stages of touch processing are also involved in the automatic coding of the affective consequences of observed touch and to which extent they show overlapping activation for somatosensory experiences of self and others. In order to investigate these issues, in the present fMRI study, healthy participants either experienced touch or watched videos depicting other individuals' inanimate and animate/social touch experiences. Essentially, a distinction can be made between exteroceptive and interoceptive components of touch processing, involved with physical stimulus characteristics and internal feeling states, respectively. Consistent with this distinction, a specific negative modulation was found in the posterior insula by the mere visual perception of other individuals' social or affective cutaneous experiences, compared to neutral inanimate touch. On the other hand, activation in secondary somatosensory and posterior superior temporal regions, strongest for the most intense stimuli, seemed more dependent on the observed physical stimulus characteristics. In contrast to the detected vicarious activation in somatosensory regions, opposite activation patterns for the experience (positive modulation) and observation (negative modulation) of touch suggest that the posterior insula does not reflect a shared representation of self and others' experiences. Embedded in a distributed network of brain regions underpinning a sense of the bodily self, the posterior insula rather appears to differentiate between self and other conditions when affective experiences are implicated.
The impact of ultra-high field MRI on cognitive and computational neuroimaging.
NeuroImage, 2018

The ability to measure functional brain responses non-invasively with ultra high field MRI (7 T and above) represents a unique opportunity in advancing our understanding of the human brain. Compared to lower fields (3 T and below), ultra high field MRI has an increased sensitivity, which can be used to acquire functional images with greater spatial resolution, and greater specificity of the blood oxygen level dependent (BOLD) signal to the underlying neuronal responses. Together, increased resolution and specificity enable investigating brain functions at a submillimeter scale, which so far could only be done with invasive techniques. At this mesoscopic spatial scale, perception, cognition and behavior can be probed at the level of fundamental units of neural computations, such as cortical columns, cortical layers, and subcortical nuclei. This represents a unique and distinctive advantage that differentiates ultra high from lower field imaging and that can foster a tighter link between fMRI and computational modeling of neural networks. So far, functional brain mapping at submillimeter scale has focused on the processing of sensory information and on well-known systems for which extensive information is available from invasive recordings in animals. It remains an open challenge to extend this methodology to uniquely human functions and, more generally, to systems for which animal models may be problematic. To succeed, the possibility to acquire high-resolution functional data with large spatial coverage, the availability of computational models of neural processing as well as accurate biophysical modeling of neurovascular coupling at mesoscopic scale all appear necessary.
A critical evaluation of the ubiquitin-proteasome system in Parkinson's disease.
Biochimica et biophysica acta, 2009

The evidence for impairment in the ubiquitin proteasome system (UPS) in Parkinson's disease (PD) is mounting and becoming increasingly more convincing. However, it is presently unclear whether UPS dysfunction is a cause or result of PD pathology, a crucial distinction which impedes both the understanding of disease pathogenesis and the development of effectual therapeutic approaches. Recent findings discussed within this review offer new insight and provide direction for future research to conclusively resolve this debate.
Tissue Engineering Strategies as Tools for Personalized Meningioma Treatment.
Artificial organs, 2015

Pharmacogenomics, the science of how genetic makeup influences an individual's reaction to drugs, is an innovative tool for providing critical insights into how a patient will respond to a particular treatment. In the present work, we constructed cancer-like tissues to be used as tools for determining the most effective drug for an individual patient. Using tissue engineering strategies, we generated two different solid tumor-like tissues in vitro, a neuronal tumor (meningioma) and a nonmelanoma skin cancer. Samples were tested by both histological and genetic approaches (using a comparative genomic hybridization array, and the relative World Health Organization classification of the samples was compared with the results obtained by the molecular analyses. Our data confirmed the ability of the cells to maintain their phenotype in three-dimensional scaffolds as well as the strong relationship between chromosomal alterations and histological malignancy grades. We then validated the in vitro construction of tumor-like tissues as a potential tool for developing personalized drug treatments.
COX-2-Derived Prostaglandin E2 Produced by Pyramidal Neurons Contributes to Neurovascular Coupling in the Rodent Cerebral Cortex.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015

Vasodilatory prostaglandins play a key role in neurovascular coupling (NVC), the tight link between neuronal activity and local cerebral blood flow, but their precise identity, cellular origin and the receptors involved remain unclear. Here we show in rats that NMDA-induced vasodilation and hemodynamic responses evoked by whisker stimulation involve cyclooxygenase-2 (COX-2) activity and activation of the prostaglandin E2 (PgE2) receptors EP2 and EP4. Using liquid chromatography-electrospray ionization-tandem mass spectrometry, we demonstrate that PgE2 is released by NMDA in cortical slices. The characterization of PgE2 producing cells by immunohistochemistry and single-cell reverse transcriptase-PCR revealed that pyramidal cells and not astrocytes are the main cell type equipped for PgE2 synthesis, one third expressing COX-2 systematically associated with a PgE2 synthase. Consistent with their central role in NVC, in vivo optogenetic stimulation of pyramidal cells evoked COX-2-dependent hyperemic responses in mice. These observations identify PgE2 as the main prostaglandin mediating sensory-evoked NVC, pyramidal cells as their principal source and vasodilatory EP2 and EP4 receptors as their targets.