rudyvdbrink/CitationDatabase huggingface dataset:
Deciphering the lithium transcriptome: microarray profiling of lithium-modulated gene expression in human neuronal cells.
Neuroscience, 2008

The mechanisms underlying lithium's therapeutic efficacy in the chronic treatment of bipolar disorder are not clearly understood. Useful insights can be obtained by identifying genes that are differentially regulated during chronic lithium treatment. Toward this end, we have used microarray technology to identify mRNAs that are differentially expressed in a human neuronal cell line that has been continuously maintained in therapeutic levels of lithium for 33 days. Significantly, unlike other transcriptomes where predominantly rodent cells were used and a limited number of genes probed, we have used human cells probed with more extensive 44,000 gene microarrays. A total of 671 differentially regulated transcripts, after correcting for false discovery rates, were identified, of which 347 and 324, respectively, were found to be up- and downregulated. Peroxiredoxin 2 (PRDX2), an antioxidant enzyme, was the most upregulated while tribbles homolog 3 (TRB3), a pro-apoptotic protein, was the most downregulated, implying a beneficial effect of lithium on neuronal cells. Several of the most highly regulated genes are novel, uncharacterized and encode proteins of unknown function. Differentially expressed genes associated with phosphoinositide metabolism include those encoding phosphatidyl inositol 4-phosphate 5-kinase type II alpha (PIP5K2A), WD repeat domain, phosphoinositide interacting 1 protein (WIPI49), tribbles homolog 3 (TRB3) and sorting nexin 14 (SNX14). A protein interactome using some of the saliently regulated genes identified protein kinase C (PKC) as a major target for lithium action while a global analysis of all 671 differentially expressed genes identified the mitogen-activated protein kinase pathway as the most regulated. The list of highly regulated genes, besides encoding putative targets for antimanic agents, should prove useful in defining novel pathways, or to better understand the mechanisms, underlying the mood stabilization process.
Temporal Context affects interval timing at the perceptual level.
Scientific reports, 2020

There is now ample evidence that when observers are asked to estimate features of an object they take into account recent stimulation history and blend the current sensory evidence with the recent stimulus intensity according to their reliability. Most of this evidence has been obtained via estimation or production paradigms both of which entail a conspicuous post-perceptual decision stage. So it is an unsolved question, as to whether the trace of previous stimulation contributes at the decision stage or as early as the perceptual stage. To this aim we focused on duration judgments, which typically exhibit strong central tendency effects and asked a duration comparison between two intervals, one of which characterized by high uncertainty. We found that the perceived duration of this interval regressed toward the average duration, demonstrating a genuine perceptual bias. Regression did not transfer between the visual and the auditory modality, indicating it is modality specific, but generalized across passively observed and actively produced intervals. These findings suggest that temporal central tendency effects modulate how long an interval appears to us and that integration of current sensory evidence can occur as early as in the sensory systems.
Chronic CXCL10 alters neuronal properties in rat hippocampal culture.
Journal of neuroimmunology, 2009

The chemokine CXCL10 is expressed in the central nervous system (CNS) during neuroinflammatory conditions. Neurons express CXCR3, the receptor for CXCL10, and neuronal function has been shown to be altered by acute exposure to CXCL10. Little is known about the effects of chronic exposure to CXCL10 on neuronal function. Results from our studies show that chronic exposure of cultured rat hippocampal neurons to CXCL10 results in altered levels of protein for GABA and glutamate receptors and altered synaptic network activity. These effects of CXCL10 may contribute to altered CNS function that occurs in some chronic neuroinflammatory conditions.
Phylogenetic variation in cortical layer II immature neuron reservoir of mammals.
eLife, 2020

The adult mammalian brain is mainly composed of mature neurons. A limited amount of stem cell-driven neurogenesis persists in postnatal life and is reduced in large-brained species. Another source of immature neurons in adult brains is cortical layer II. These cortical immature neurons (cINs) retain developmentally undifferentiated states in adulthood, though they are generated before birth. Here, the occurrence, distribution and cellular features of cINs were systematically studied in 12 diverse mammalian species spanning from small-lissencephalic to large-gyrencephalic brains. In spite of well-preserved morphological and molecular features, the distribution of cINs was highly heterogeneous, particularly in neocortex. While virtually absent in rodents, they are present in the entire neocortex of many other species and their linear density in cortical layer II generally increased with brain size. These findings suggest an evolutionary developmental mechanism for plasticity that varies among mammalian species, granting a reservoir of young cells for the cerebral cortex.
Enhanced GABAergic activity in the mouse primary somatosensory cortex is insufficient to alleviate chronic pain behavior with reduced expression of neuronal potassium-chloride cotransporter.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012

The correct balance between excitation and inhibition is crucial for brain function and disrupted in several pathological conditions. Excitatory neuronal circuits in the primary somatosensory cortex (S1) are modulated by local inhibitory neurons with the balance of this excitatory and inhibitory activity important for function. The activity of excitatory layer 2/3 neurons (L2/3) in the S1 cortex is increased in chronic pain, but it is not known how the local interneurons, nor the balance between excitation and inhibition, may change in chronic pain. Using in vivo two-photon calcium imaging and electrophysiology, we report here that the response of L2/3 local inhibitory neurons to both sensory stimulation and to layer 4 electrical stimulation increases in inflammatory chronic pain. Local application into L2/3 of a GABA(A) receptor blocker further enhanced the activity of S1 excitatory neurons and reduced pain thresholds, whereas local application of the GABA(A) receptor modulators (muscimol and diazepam) transiently alleviated the allodynia. This illustrates the importance of the local inhibitory pathways in chronic pain sensation. A reduction in the expression and function of the potassium-chloride cotransporter 2 occurred during chronic pain, which reduces the efficacy of the inhibitory inputs to L2/3 excitatory neurons. In summary, both excitatory and inhibitory neuronal activities in the S1 are enhanced in the chronic pain model, but the increased inhibition is insufficient to completely counterbalance the increased excitation and alleviate the symptoms of chronic pain.
Brains in the city: Neurobiological effects of urbanization.
Neuroscience and biobehavioral reviews, 2015

With a majority of humans now living in cities, strategic research is necessary to elucidate the impact of this evolutionarily unfamiliar habitat on neural functions and well-being. In this review, both rodent and human models are considered in the evaluation of the changing physical and social landscapes associated with urban dwellings. Animal models assessing increased exposure to artificial physical elements characteristic of urban settings, as well as exposure to unnatural sources of light for extended durations, are reviewed. In both cases, increased biomarkers of mental illnesses such as major depression have been observed. Additionally, applied human research emphasizing the emotional impact of environmental threats associated with urban habitats is considered. Subjects evaluated in an inner-city hospital reveal the impact of combined specific genetic vulnerabilities and heightened stress responses in the expression of posttraumatic stress disorder. Finally, algorithm-based models of cities have been developed utilizing population-level analyses to identify risk factors for psychiatric illness. Although complex, the use of multiple research approaches, as described herein, results in an enhanced understanding of urbanization and its far-reaching effects--confirming the importance of continued research directed toward the identification of putative risk factors associated with psychiatric illness in urban settings.
Inflammation and dimensions of reward processing following exposure to the influenza vaccine.
Psychoneuroendocrinology, 2019

Alterations in reward processing are a central feature of depression and may be influenced by inflammation. Indeed, inflammation is associated with deficits in reward-related processes in animal models and with dysregulation in reward-related neural circuitry in humans. However, the downstream behavioral manifestations of such impairments are rarely examined in humans.
Effects of behavioural activation on the neural basis of other perspective self-referential processing in subthreshold depression: a functional magnetic resonance imaging study.
Psychological medicine, 2017

It has been demonstrated that negatively distorted self-referential processing, in which individuals evaluate one's own self, is a pathogenic mechanism in subthreshold depression that has a considerable impact on the quality of life and carries an elevated risk of developing major depression. Behavioural activation (BA) is an effective intervention for depression, including subthreshold depression. However, brain mechanisms underlying BA are not fully understood. We sought to examine the effect of BA on neural activation during other perspective self-referential processing in subthreshold depression.
Cerebral accumulation of dietary derivable plant sterols does not interfere with memory and anxiety related behavior in Abcg5-/- mice.
Plant foods for human nutrition (Dordrecht, Netherlands), 2011

Plant sterols such as sitosterol and campesterol are frequently applied as functional food in the prevention of atherosclerosis. Recently, it became clear that plasma derived plant sterols accumulate in murine brains. We questioned whether plant sterols in the brain are associated with alterations in brain cholesterol homeostasis and subsequently with brain functions. ATP binding cassette (Abc)g5-/- mice, a phytosterolemia model, were compared to Abcg5+/+ mice for serum and brain plant sterol accumulation and behavioral and cognitive performance. Serum and brain plant sterol concentrations were respectively 35-70-fold and 5-12-fold increased in Abcg5-/- mice (P<0.001). Plant sterol accumulation resulted in decreased levels of desmosterol (P<0.01) and 24(S)-hydroxycholesterol (P<0.01) in the hippocampus, the brain region important for learning and memory functions, and increased lanosterol levels (P<0.01) in the cortex. However, Abcg5-/- and Abcg5+/+ displayed no differences in memory functions or in anxiety and mood related behavior. The swimming speed of the Abcg5-/- mice was slightly higher compared to Abcg5+/+ mice (P<0.001). In conclusion, plant sterols in the brains of Abcg5-/- mice did have consequences for brain cholesterol metabolism, but did not lead to an overt phenotype of memory or anxiety related behavior. Thus, our data provide no contra-indication for nutritional intake of plant sterol enriched nutrition.
Comparing internet-delivered cognitive therapy and behavior therapy with telephone support for insomnia disorder: a randomized controlled trial.
Sleep, 2020

Our aim was to compare the effects of Internet-delivered cognitive therapy (CT) and behavior therapy (BT) against a waitlist (WL) condition to better understand their unique contribution in the treatment of insomnia.
Age-related sensory decline mediates the Sound-Induced Flash Illusion: Evidence for reliability weighting models of multisensory perception.
Scientific reports, 2019

Perception of our world is proposed to arise from combining multiple sensory inputs according to their relative reliability. We tested multisensory processes in a large sample of 2920 older adults to assess whether sensory ability mediates age-related changes in perception. Participants completed a test of audio-visual integration, the Sound Induced Flash Illusion (SIFI), alongside measures of visual (acuity, contrast sensitivity, self-reported vision and visual temporal discrimination (VTD)) and auditory (self-reported hearing and auditory temporal discrimination (ATD)) function. Structural equation modelling showed that SIFI susceptibility increased with age. This was mediated by visual acuity and self-reported hearing: better scores on these measures predicted reduced and stronger SIFI susceptibility, respectively. Unexpectedly, VTD improved with age and predicted increased SIFI susceptibility. Importantly, the relationship between age and SIFI susceptibility remained significant, even when considering mediators. A second model showed that, with age, visual 'gain' (the benefit of congruent auditory information on visual judgements) was predicted by ATD: better ATD predicted stronger visual gain. However, neither age nor SIFI susceptibility were directly associated with visual gain. Our findings illustrate, in the largest sample of older adults to date, how multisensory perception is influenced, but not fully accounted for, by age-related changes in unisensory abilities.
Intracellular signaling in M-CSF-induced microglia activation: role of Iba1.
Glia, 2002

Microglia are reactively activated by various environmental stimulations caused by brain injury or disease. Activated microglia exhibit morphological transformation, proliferation, migration, phagocytosis, and the production of bioactive molecules. Various molecules are reported and suggested to activate microglia. Among them, macrophage-colony-stimulating factor (M-CSF) is considered one of the most convincing candidates responsible for maintaining activation properties of microglia. Therefore, the focus of the present study is on intracellular molecular events that arise downstream of M-CSF stimulation. M-CSF activates its receptor, Fms tyrosine kinase, and Fms sequentially activates a number of signaling molecules, including PI3K or phospholipase Cgamma (PLCgamma). Stimulation of continuing signaling cascades results in the activation of a small GTPase, Rac, the key molecule in microglia activation. Rac is known to be activated downstream of receptor tyrosine kinases and to regulate reorganization of the actin cytoskeleton, which profoundly underlies the above-mentioned properties of activated microglia. Iba1, a macrophage/microglia-specific calcium-binding protein, was identified by our group and was shown to be involved in the Rac signaling pathway. Further, we introduce a novel signaling pathway in which Rac is activated, dependent on PLCgamma and Iba1. However, to understand the molecular details of microglia activation, future work is required.
Specialized functions of Nav1.5 and Nav1.9 channels in electrogenesis of myenteric neurons in intact mouse ganglia.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014

Voltage-gated sodium (Nav) channels play a central role in gastrointestinal physiology because they transmit depolarizing impulses in enteric neurons, thereby enabling the coordination of intestinal motility. However, little is known about the ion channel machinery that specifies firing pattern of enteric neurons. Here, we used in situ patch-clamp recording of myenteric neurons from mice to define functionally the Nav channel subtypes responsible for the electrical signature of myenteric neurons. We found that mouse myenteric neurons exhibit two types of tetrodotoxin-resistant Na(+) currents: an early inactivating Na(+) current (INaT) and a persistent Na(+) current (INaP). INaT was encountered in all myenteric neurons, whereas INaP was preferentially found in Dogiel type II sensory neurons. Knock-out mouse studies, in combination with pharmacological assays, indicate that INaT is carried by the Scn5a-encoded "cardiac" Nav1.5, whereas INaP is attributed to the Scn11a-encoded Nav1.9. Current-clamp experiments show that Nav1.9 flows at subthreshold voltages, generating tonic firing. In addition, action potential (AP) clamp reveals that Nav1.5 contributes to the upstroke velocity of APs, whereas Nav1.9, which remains active during the falling phase, opposes AP repolarization. We developed a computational model of a Dogiel type II myenteric neuron that successfully reproduces all experimentally observed phenomena and highlights the differential roles of Nav1.5 and Nav1.9 in the control of excitability. Our data illustrate how excitability can be finely tuned to provide specific firing templates by the selective deployment of Nav1.5 and Nav1.9 isoforms. We propose that Nav-dependent ENS disorders of excitability may play important roles in the pathogenesis of digestive diseases.
Detecting tones in complex auditory scenes.
NeuroImage, 2015

In everyday life, our auditory system is bombarded with many signals in complex auditory scenes. Limited processing capacities allow only a fraction of these signals to enter perceptual awareness. This magnetoencephalography (MEG) study used informational masking to identify the neural mechanisms that enable auditory awareness. On each trial, participants indicated whether they detected a pair of sequentially presented tones (i.e., the target) that were embedded within a multi-tone background. We analysed MEG activity for 'hits' and 'misses', separately for the first and second tones within a target pair. Comparing physically identical stimuli that were detected or missed provided insights into the neural processes underlying auditory awareness. While the first tone within a target elicited a stronger early P50m on hit trials, only the second tone evoked a negativity at 150 ms, which may index segregation of the tone pair from the multi-tone background. Notably, a later sustained deflection peaking around 300 and 500 ms (P300m) was the only component that was significantly amplified for both tones, when they were detected pointing towards its key role in perceptual awareness. Additional Dynamic Causal Modelling analyses indicated that the negativity at 150 ms underlying auditory stream segregation is mediated predominantly via changes in intrinsic connectivity within auditory cortices. By contrast, the later P300m response as a signature of perceptual awareness relies on interactions between parietal and auditory cortices. In conclusion, our results suggest that successful detection and hence auditory awareness of a two-tone pair within complex auditory scenes relies on recurrent processing between auditory and higher-order parietal cortices.
Pipeline Embolization Device with or without Adjunctive Coil Embolization: Analysis of Complications from the IntrePED Registry.
AJNR. American journal of neuroradiology, 2016

Flow diversion to treat cerebral aneurysms has revolutionized neurointerventional surgery. Because the addition of coils potentially increases the time and complexity of endovascular procedures, we sought to determine whether adjunctive coil use is associated with an increase in complications. Patients in the International Retrospective Study of Pipeline Embolization Device registry were divided into those treated with the Pipeline Embolization Device alone (n = 689 patients; n = 797 aneurysms; mean aneurysm size, 10.3 ± 7.6 mm) versus those treated with the Pipeline Embolization Device and concurrent coil embolization (n = 104 patients; n = 109 aneurysms; mean aneurysm size, 13.6 ± 7.8 mm). Patient demographics and aneurysm characteristics were examined. Rates of neurologic morbidity and mortality were compared between groups. The Pipeline Embolization Device with versus without coiling required a significantly longer procedure time (135.8 ± 63.9 versus 96.7 ± 46.2 min; P < .0001) and resulted in higher neurological morbidity (12.5% versus 7.8%; P = .13). These data suggest that either strategy represents an acceptable risk profile in the treatment of complex cerebral aneurysms and warrants further investigation.
Sex-dependent effects of MC4R genotype on HPA axis tone: implications for stress-associated cardiometabolic disease.
Stress (Amsterdam, Netherlands), 2019

The melanocortin-4 receptor (MC4R) facilitates hypothalamic-pituitary-adrenocortical (HPA) axis responses to acute stress in male rodents and is a well known to regulator of energy balance. Mutations in the MC4R is the most common monogenic cause of obesity in humans and has been associated with sex-specific effects, but whether stress regulation by the MC4R is sex-dependent, and whether the MC4R facilitates HPA responses to chronic stress, is unknown. We hypothesized that MC4R-signaling contributes to HPA axis dysregulation and metabolic pathophysiology following chronic stress exposure. We measured changes in energy balance, HPA axis tone, and vascular remodeling during chronic variable stress (CVS) in male and female rats with MC4R loss-of-function. Rats were placed into three groups (
How Eye Dominance Strength Modulates the Influence of a Distractor on Saccade Accuracy.
Investigative ophthalmology & visual science, 2016

Neuroimaging studies have shown that the dominant eye is linked preferentially to the ipsilateral primary visual cortex. However, its role in perception still is misunderstood. We examined the influence of eye dominance and eye dominance strength on saccadic parameters, contrasting stimulations presented in the two hemifields.
Bariatric Surgery Is Accompanied by Changes in Extracellular Vesicle-Associated and Plasma Fatty Acid Binding Protein 4.
Obesity surgery, 2018

Bariatric surgery markedly reduces fat mass with beneficial effects on cardiometabolic health but the mechanisms involved are not fully understood. Extracellular vesicles (EVs) are secreted by a variety of cells, including adipocytes, and may mediate some of these benefits. However, the effects of bariatric surgery on circulating EVs are unclear.
Usefulness of event-related potentials in the assessment of mild cognitive impairment.
BMC neuroscience, 2008

The aim of this study was to determine if changes in latencies and amplitudes of the major waves of Auditory Event-Related Potentials (AERP), correlate with memory status of patients with mild cognitive impairment (MCI) and conversion to Alzheimer's disease (AD). 91 patients with MCI (mean +/- SD age = 66.6 +/- 5.4, MMSE score = 27.7) and 30 age-matched healthy control (AMHC) subjects (mean +/- SD age = 68.9 +/- 9.9) were studied. 54 patients were re-examined after an average period of 14(+/- 5.2) months. During this time period 5 patients converted to AD. Between-group differences in latency and amplitude of the major AERP waves (N200, P300 and Slow Wave) were determined. Within each group, correlation coefficients (CC) between these characteristics of the different AERP waves were calculated. Finally, for patients, CCs were determined among each AERP wave and their age and MMSE scores. Confirmatory factor analysis (CFA) was used to examine the underlying structure of waveforms both in the control and the patient groups.
Predictors of Long-Term Psychosocial Functioning and Health-Related Quality of Life in Children and Adolescents With Prior Concussions.
Journal of the International Neuropsychological Society : JINS, 2018

Individual differences in long-term psychosocial functioning after concussions in children and adolescents are poorly understood. The aim of the study was to investigate potential predictors of long-term psychosocial functioning and health-related quality of life in youth after prior concussion.