rudyvdbrink/CitationDatabase huggingface dataset:
The origin of NMDA receptor hypofunction in schizophrenia.
Pharmacology & therapeutics, 2020

N-methyl-d-aspartate (NMDA) receptor (NMDAR) hypofunction plays a key role in pathophysiology of schizophrenia. Since NMDAR hypofunction has also been reported in autism, Alzheimer's disease and cognitive dementia, it is crucial to identify the location, timing, and mechanism of NMDAR hypofunction for schizophrenia for better understanding of disease etiology and for novel therapeutic intervention. In this review, we first discuss the shared underlying mechanisms of NMDAR hypofunction in NMDAR antagonist models and the anti-NMDAR autoantibody model of schizophrenia and suggest that NMDAR hypofunction could occur in GABAergic neurons in both models. Preclinical models using transgenic mice have shown that NMDAR hypofunction in cortical GABAergic neurons, in particular parvalbumin-positive fast-spiking interneurons, in the early postnatal period confers schizophrenia-related phenotypes. Recent studies suggest that NMDAR hypofunction can also occur in PV-positive GABAergic neurons with alterations of NMDAR-associated proteins, such as neuregulin/ErbB4, α7nAChR, and serine racemase. Furthermore, several environmental factors, such as oxidative stress, kynurenic acid and hypoxia, may also potentially elicit NMDAR hypofunction in GABAergic neurons in early postnatal period. Altogether, the studies discussed here support a central role for GABAergic abnormalities in the context of NMDAR hypofunction. We conclude by suggesting potential therapeutic strategies to improve the function of fast-spiking neurons.
Effect of resistance exercise on serum levels of growth factors in humans.
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme, 2010

Studies have shown that, depending on intensity, endurance exercise increases neurotrophins and thereby induces neuroplasticity. However, data on the effect of acute resistance exercise at different intensities on neurotrophins is not yet available. Thus, we conducted 2 trials to determine the serum concentrations of brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), and insulin-like growth factor (IGF-1) before and after a low or high intensity resistance exercise in 11 healthy humans. Exercise load was related to 3 repetitions of maximal effort isokinetic work involving knee extension under alternating concentric and eccentric conditions for muscle work at a velocity of 60°s-1 registered during a familiarization session. The torque angle diagrams from these 3 repetitions were averaged and displayed as target curves in the test sessions, the intensity of resistance exercise was set at 40% (trial: R1) or 110% (trial: R2) of the averaged individual maximal effort curve, respectively. After resistance exercise, serum IGF-1 was increased significantly (p<0.01) by 28% in R1 and 16% in R2 compared to pre-exercise levels. Resistance exercise did not increase serum VEGF at any time point. Serum BDNF increased during exercise compared to post-exercise, but did not achieve significant difference from pre-exercise values. The present study shows that either low or high resistance exercise increases levels of IGF-1, but not of BDNF or VEGF. This finding is of importance for health promotion by means of resistance exercise because circulating serum IGF-1 has been demonstrated to mediate positive effects of exercise on brain functions.
New strategies for preventing epileptogenesis: perspective and overview.
Neuroscience letters, 2011

Epilepsy is a common disorder with a major negative impact on patient quality of life, yet treatment so far is directed mainly at blocking the symptoms-epileptic seizures, not the underlying cause. In recent years, investigation of epilepsy development or epileptogenesis has yielded new insights into potential therapies that may ultimately prevent epilepsy before it starts. In this special issue of Neuroscience Letters the latest advances in the field are brought together, summarizing: (1) important animal models in both primary and secondary epilepsies, (2) promising biomarkers for monitoring epileptogenesis, (3) cellular and molecular mechanisms which may serve as viable targets for therapy, and (4) translational approaches to human clinical trials. Bringing together these intriguing new approaches to treating epilepsy as a preventable disorder will hopefully soon make symptomatic treatment of epilepsy unnecessary in most patients.
Characterization and Cellular Internalization of Spherical Cellulose Nanocrystals (CNC) into Normal and Cancerous Fibroblasts.
Materials (Basel, Switzerland), 2019

The aim was to isolate cellulose nanocrystals (CNC) from commercialized oil palm empty fruit bunch cellulose nanofibre (CNF) through sulphuric acid hydrolysis and explore its safeness as a potential nanocarrier. Successful extraction of CNC was confirmed through a field emission scanning electron microscope (FESEM) and attenuated total reflection Fourier transmission infrared (ATR-FTIR) spectrometry analysis. For subsequent cellular uptake study, the spherical CNC was covalently tagged with fluorescein isothiocyanate (FITC), resulting in negative charged FITC-CNC nanospheres with a dispersity (Ð) of 0.371. MTT assay revealed low degree cytotoxicity for both CNC and FITC-CNC against C6 rat glioma and NIH3T3 normal fibroblasts up to 50 µg/mL. FITC conjugation had no contribution to the particle's toxicity. Through confocal laser scanning microscope (CLSM), synthesized FITC-CNC manifested negligible cellular accumulation, indicating a poor non-selective adsorptive endocytosis into studied cells. Overall, an untargeted CNC-based nanosphere with less cytotoxicity that posed poor selectivity against normal and cancerous cells was successfully synthesized. It can be considered safe and suitable to be developed into targeted nanocarrier.
Evolution of Endothelin signaling and diversification of adult pigment pattern in Danio fishes.
PLoS genetics, 2018

Fishes of the genus Danio exhibit diverse pigment patterns that serve as useful models for understanding the genes and cell behaviors underlying the evolution of adult form. Among these species, zebrafish D. rerio exhibit several dark stripes of melanophores with sparse iridophores that alternate with light interstripes of dense iridophores and xanthophores. By contrast, the closely related species D. nigrofasciatus has an attenuated pattern with fewer melanophores, stripes and interstripes. Here we demonstrate species differences in iridophore development that presage the fully formed patterns. Using genetic and transgenic approaches we identify the secreted peptide Endothelin-3 (Edn3)-a known melanogenic factor of tetrapods-as contributing to reduced iridophore proliferation and fewer stripes and interstripes in D. nigrofasciatus. We further show the locus encoding this factor is expressed at lower levels in D. nigrofasciatus owing to cis-regulatory differences between species. Finally, we show that functions of two paralogous loci encoding Edn3 have been partitioned between skin and non-skin iridophores. Our findings reveal genetic and cellular mechanisms contributing to pattern differences between these species and suggest a model for evolutionary changes in Edn3 requirements for pigment patterning and its diversification across vertebrates.
Individual recovery profiles of manual dexterity, and relation to corticospinal lesion load and excitability after stroke -a longitudinal pilot study.
Neurophysiologie clinique = Clinical neurophysiology, 2019

In this longitudinal pilot study, we investigated how manual dexterity recovery was related to corticospinal tract (CST) injury and excitability, in six patients undergoing conventional rehabilitation.
Effects of acute tryptophan depletion on memory, attention and executive functions: a systematic review.
Neuroscience and biobehavioral reviews, 2009

The serotonergic system is implicated in the regulation of mood and cognition. Acute tryptophan depletion (ATD) is an experimental procedure for lowering central serotonin levels. Here, the effects of ATD on psychomotor processing, declarative memory, working memory, executive functions and attention are discussed. The most robust finding is that ATD impairs the consolidation of episodic memory for verbal information. Semantic memory appears to be unaffected by ATD although a limited variety of tasks examined effects in this domain. Similarly, evidence suggests ATD does not influence verbal, spatial and affective working memory. Most studies investigating effects on executive functions have produced non-specific or negative findings. In terms of attention, ATD either does not affect or may improve focused attention and ATD likely does not impact sustained and divided attention or attentional set-shifting. Although ATD is known to affect mood in certain vulnerable populations, the effects of ATD on cognition in non-vulnerable participants are independent of mood changes. Suggestions for future directions and implications for psychiatric illnesses are discussed.
Past visual experiences weigh in on body size estimation.
Scientific reports, 2018

Body size is a salient marker of physical health, with extremes implicated in various mental and physical health issues. It is therefore important to understand the mechanisms of perception of body size of self and others. We report a novel technique we term the bodyline, based on the numberline technique in numerosity studies. One hundred and three young women judged the size of sequentially presented female body images by positioning a marker on a line, delineated with images of extreme sizes. Participants performed this task easily and well, with average standard deviations less than 6% of the total scale. Critically, judgments of size were biased towards the previously viewed body, demonstrating that serial dependencies occur in the judgment of body size. The magnitude of serial dependence was well predicted by a simple Kalman-filter ideal-observer model, suggesting that serial dependence occurs in an optimal, adaptive way to improve performance in size judgments.
Multifactorial determinants of the neurocognitive effects of electroconvulsive therapy.
The journal of ECT, 2014

For many patients with neuropsychiatric illnesses, standard psychiatric treatments with mono or combination pharmacotherapy, psychotherapy, and transcranial magnetic stimulation are ineffective. For these patients with treatment-resistant neuropsychiatric illnesses, a main therapeutic option is electroconvulsive therapy (ECT). Decades of research have found ECT to be highly effective; however, it can also result in adverse neurocognitive effects. Specifically, ECT results in disorientation after each session, anterograde amnesia for recently learned information, and retrograde amnesia for previously learned information. Unfortunately, the neurocognitive effects and underlying mechanisms of action of ECT remain poorly understood. The purpose of this paper was to synthesize the multiple moderating and mediating factors that are thought to underlie the neurocognitive effects of ECT into a coherent model. Such factors include demographic and neuropsychological characteristics, neuropsychiatric symptoms, ECT technical parameters, and ECT-associated neurophysiological changes. Future research is warranted to evaluate and test this model, so that these findings may support the development of more refined clinical seizure therapy delivery approaches and efficacious cognitive remediation strategies to improve the use of this important and widely used intervention tool for neuropsychiatric diseases.
Human mesostriatal response tracks motivational tendencies under naturalistic goal conflict.
Social cognitive and affective neuroscience, 2016

Goal conflict situations, involving the simultaneous presence of reward and punishment, occur commonly in real life, and reflect well-known individual differences in the behavioral tendency to approach or avoid. However, despite accumulating neural depiction of motivational processing, the investigation of naturalistic approach behavior and its interplay with individual tendencies is remarkably lacking. We developed a novel ecological interactive scenario which triggers motivational behavior under high or low goal conflict conditions. Fifty-five healthy subjects played the game during a functional magnetic resonance imaging scan. A machine-learning approach was applied to classify approach/avoidance behaviors during the game. To achieve an independent measure of individual tendencies, an integrative profile was composed from three established theoretical models. Results demonstrated that approach under high relative to low conflict involved increased activity in the ventral tegmental area (VTA), peri-aquaductal gray, ventral striatum (VS) and precuneus. Notably, only VS and VTA activations during high conflict discriminated between approach/avoidance personality profiles, suggesting that the relationship between individual personality and naturalistic motivational tendencies is uniquely associated with the mesostriatal pathway. VTA-VS further demonstrated stronger coupling during high vs low conflict. These findings are the first to unravel the multilevel relationship among personality profile, approach tendencies in naturalistic set-up and their underlying neural manifestation, thus enabling new avenues for investigating approach-related psychopathologies.
Neural dissociation between visual awareness and spatial attention.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2008

To what extent does what we consciously see depend on where we attend to? Psychologists have long stressed the tight relationship between visual awareness and spatial attention at the behavioral level. However, the amount of overlap between their neural correlates remains a matter of debate. We recorded magnetoencephalographic signals while human subjects attended toward or away from faint stimuli that were reported as consciously seen only half of the time. Visually identical stimuli could thus be attended or not and consciously seen or not. Although attended stimuli were consciously seen slightly more often than unattended ones, the factorial analysis of stimulus-induced oscillatory brain activity revealed distinct and independent neural correlates of visual awareness and spatial attention at different frequencies in the gamma range (30-150 Hz). Whether attended or not, consciously seen stimuli induced increased mid-frequency gamma-band activity over the contralateral visual cortex, whereas spatial attention modulated high-frequency gamma-band activity in response to both consciously seen and unseen stimuli. A parametric analysis of the data at the single-trial level confirmed that the awareness-related mid-frequency activity drove the seen-unseen decision but also revealed a small influence of the attention-related high-frequency activity on the decision. These results suggest that subjective visual experience is shaped by the cumulative contribution of two processes operating independently at the neural level, one reflecting visual awareness per se and the other reflecting spatial attention.
Mutations in the transmembrane helix S6 of domain IV confer cockroach sodium channel resistance to sodium channel blocker insecticides and local anesthetics.
Insect biochemistry and molecular biology, 2015

Indoxacarb and metaflumizone are two sodium channel blocker insecticides (SCBIs). They preferably bind to and trap sodium channels in the slow-inactivated non-conducting state, a mode of action similar to that of local anesthetics (LAs). Recently, two sodium channel mutations, F1845Y (F(4i15)Y) and V1848I (V(4i18)I), in the transmembrane segment 6 of domain IV (IVS6), were identified to be associated with indoxacarb resistance in Plutella xylostella. F(4i15) is known to be critical for the action of LAs on mammalian sodium channels. Previously, mutation F(4i15)A in a cockroach sodium channel, BgNav1-1a, has been shown to reduce the action of lidocaine, a LA, but not the action of SCBIs. In this study, we introduced mutations F(4i15)Y and V(4i18)A/I individually into the cockroach sodium channel, BgNav1-1a, and conducted functional analysis of the three mutants in Xenopus oocytes. We found that both the F(4i15)Y and V(4i18)I mutations reduced the inhibition of sodium current by indoxacarb, DCJW (an active metabolite of indoxacarb) and metaflumizone. F(4i15)Y and V(4i18)I mutations also reduced the use-dependent block of sodium current by lidocaine. In contrast, substitution V(4i18)A enhanced the action metaflumizone and lidocaine. These results show that both F(4i15)Y and V(4i18)I mutations may contribute to target-site resistance to SCBIs, and provide the first molecular evidence for common amino acid determinants on insect sodium channels involved in action of SCBIs and LA.
Network outcome analysis identifies difficulty initiating sleep as a primary target for prevention of depression: a 6-year prospective study.
Sleep, 2020

Major depressive disorder (MDD) is the leading cause of disability worldwide. Its high recurrence rate calls for prevention of first-onset MDD. Although meta-analysis suggested insomnia as the strongest modifiable risk factor, previous studies insufficiently addressed that insomnia might also occur as a residual symptom of unassessed prior depression, or as a comorbid complaint secondary to other depression risks.
Increased decision thresholds trigger extended information gathering across the compulsivity spectrum.
Translational psychiatry, 2017

Indecisiveness and doubt are cognitive phenotypes of compulsive disorders, including obsessive-compulsive disorder. Little is known regarding the cognitive mechanisms that drive these behaviours across a compulsivity spectrum. Here, we used a sequential information gathering task to study indecisiveness in subjects with high and low obsessive-compulsive scores. These subjects were selected from a large population-representative database, and matched for intellectual and psychiatric factors. We show that high compulsive subjects sampled more information and performed better when sampling was cost-free. When sampling was costly, both groups adapted flexibly to reduce their information gathering. Computational modelling revealed that increased information gathering behaviour could be explained by higher decision thresholds that, in turn, were driven by a delayed emergence of impatience or urgency. Our findings show that indecisiveness generalises to a compulsivity spectrum beyond frank clinical disorder, and this behaviour can be explained within a decision-theoretic framework as arising from an augmented decision threshold associated with an attenuated urgency signal.
Multiple Sclerosis: Associations Between Physical Disability and Depression Are Not Mediated by Self-Reported Physical Activity.
Perceptual and motor skills, 2017

This study investigated the interrelatedness of physical disability, physical activity, and depression among patients with multiple sclerosis (MS). We hypothesized that self-reported physical activity would mediate the effect of disability on depressive symptoms. Twenty-seven patients with MS (mean age: 49 years; 44.5% females) completed self-rating scales covering sociodemographic variables, intake of antidepressants, physical activity, and symptoms of depression; disability was measured by the Expanded Disability Status Scale. We found a higher level of disability to be significantly associated with more symptoms of depression. While higher reported physical activity was descriptively associated with lower depression scores and unrelated to Expanded Disability Status Scale, physical activity levels did not mediate the effect of disability on depressive symptoms.
Major Depressive Disorder and Dysthymia at the Intersection of Nativity and Racial-Ethnic Origins.
Journal of immigrant and minority health, 2016

Immigrants often have lower rates of depression than US-natives, but longitudinal assessments across multiple racial-ethnic groups are limited. This study examined the rates of prevalent, acquired, and persisting major depression and dysthymia by nativity and racial-ethnic origin while considering levels of acculturation, stress, and social ties. Data from the National Epidemiologic Survey on Alcohol and Related Conditions were used to model prevalence and 3-year incidence/persistence of major depression and dysthymia (DSM-IV diagnoses) using logistic regression. Substantive factors were assessed using standardized measures. The rates of major depression were lower for most immigrants, but differences were noted by race-ethnicity and outcome. Furthermore, immigrants had higher prevalence but not incidence of dysthymia. The associations between substantive factors and outcomes were mixed. This study describes and begins to explain immigrant trajectories of major depression and dysthymia over a 3-year period. The continuing research challenges and future directions are discussed.
Outcome of cell suspension allografts in a patient with Huntington's disease.
Annals of neurology, 2018

For patients with incurable neurodegenerative disorders such as Huntington's (HD) and Parkinson's disease, cell transplantation has been explored as a potential treatment option. Here, we present the first clinicopathological study of a patient with HD in receipt of cell-suspension striatal allografts who took part in the NEST-UK multicenter clinical transplantation trial. Using various immunohistochemical techniques, we found a discrepancy in the survival of grafted projection neurons with respect to grafted interneurons as well as major ongoing inflammatory and immune responses to the grafted tissue with evidence of mutant huntingtin aggregates within the transplant area. Our results indicate that grafts can survive more than a decade post-transplantation, but show compromised survival with inflammation and mutant protein being observed within the transplant site. Ann Neurol 2018;84:950-956.
Chronic unpredictable stress induces depression-related behaviors by suppressing AgRP neuron activity.
Molecular psychiatry, 2021

Previous studies have shown that AgRP neurons in the arcuate nucleus (ARC) respond to energy deficits and play a key role in the control of feeding behavior and metabolism. Here, we demonstrate that chronic unpredictable stress, an animal model of depression, decreases spontaneous firing rates, increases firing irregularity and alters the firing properties of AgRP neurons in both male and female mice. These changes are associated with enhanced inhibitory synaptic transmission and reduced intrinsic neuronal excitability. Chemogenetic inhibition of AgRP neurons increases susceptibility to subthreshold unpredictable stress. Conversely, chemogenetic activation of AgRP neurons completely reverses anhedonic and despair behaviors induced by chronic unpredictable stress. These results indicate that chronic stress induces maladaptive synaptic and intrinsic plasticity, leading to hypoactivity of AgRP neurons and subsequently causing behavioral changes. Our findings suggest that AgRP neurons in the ARC are a key component of neural circuitry involved in mediating depression-related behaviors and that increasing AgRP neuronal activity coule be a novel and effective treatment for depression.
Expression of Galpha14 in sweet-transducing taste cells of the posterior tongue.
BMC neuroscience, 2008

"Type II"/Receptor cells express G protein-coupled receptors (GPCRs) for sweet, umami (T1Rs and mGluRs) or bitter (T2Rs), as well as the proteins for downstream signalling cascades. Transduction downstream of T1Rs and T2Rs relies on G-protein and PLCbeta2-mediated release of stored Ca2+. Whereas Galphagus (gustducin) couples to the T2R (bitter) receptors, which Galpha-subunit couples to the sweet (T1R2 + T1R3) receptor is presently not known. We utilized RT-PCR, immunocytochemistry and single-cell gene expression profiling to examine the expression of the Galphaq family (q, 11, 14) in mouse taste buds.