rudyvdbrink/CitationDatabase huggingface dataset:
β-Adrenoceptor Blockade in the Basolateral Amygdala, But Not the Medial Prefrontal Cortex, Rescues the Immediate Extinction Deficit.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2017

Early psychological interventions, such as exposure therapy, rely on extinction learning to reduce the development of stress- and trauma-related disorders. However, recent research suggests that extinction often fails to reduce fear when administered soon after trauma. This immediate extinction deficit (IED) may be due to stress-induced dysregulation of neural circuits involved in extinction learning. We have shown that systemic β-adrenoceptor blockade with propranolol rescues the IED, but impairs delayed extinction. Here we sought to determine the neural locus of these effects. Rats underwent auditory fear conditioning and then received either immediate (30 min) or delayed (24 h) extinction training. We used bilateral intracranial infusions of propranolol into either the infralimbic division of the medial prefrontal cortex (mPFC) or the basolateral amygdala (BLA) to examine the effects of β-adrenoceptor blockade on immediate and delayed extinction learning. Interestingly, intra-BLA, but not intra-mPFC, propranolol rescued the IED; animals receiving intra-BLA propranolol prior to immediate extinction showed less spontaneous recovery of fear during extinction retrieval. Importantly, this was not due to impaired consolidation of the conditioning memory. In contrast, neither intra-BLA nor intra-mPFC propranolol affected delayed extinction learning. Overall, these data contribute to a growing literature suggesting dissociable roles for key nodes in the fear extinction circuit depending on the timing of extinction relative to conditioning. These data also suggest that heightened noradrenergic activity in the BLA underlies stress-induced extinction deficits. Propranolol may be a useful adjunct to behavioral therapeutic interventions in recently traumatized individuals who are at risk for developing trauma-related disorders.
Vascular smooth muscle cell phenotypic changes in patients with Marfan syndrome.
Arteriosclerosis, thrombosis, and vascular biology, 2015

Marfan's syndrome is characterized by the formation of ascending aortic aneurysms resulting from altered assembly of extracellular matrix microfibrils and chronic tissue growth factor (TGF)-β signaling. TGF-β is a potent regulator of the vascular smooth muscle cell (VSMC) phenotype. We hypothesized that as a result of the chronic TGF-β signaling, VSMC would alter their basal differentiation phenotype, which could facilitate the formation of aneurysms. This study explores whether Marfan's syndrome entails phenotypic alterations of VSMC and possible mechanisms at the subcellular level.
Cerebellar activation related to saccadic inaccuracies.
Cerebellum (London, England), 2013

Using functional MRI, we assessed activity in the human cerebellum related to the properties of post-saccadic visual errors that drive the plasticity of saccadic eye movements. In the scanner subjects executed blocks of saccadic eye movements toward a target that could be randomly displaced during the saccade. Such an intra-saccadic shift was randomly forward or backward, and could be either small or large. Post-saccadic visual errors induced activation in several cerebellar areas. These areas included, but were not limited to, the oculomotor vermis which is known for its role in saccadic control. Large errors yielded more activation in the cerebellar hemispheres, whereas small errors induced more activation in the vermis. Forward shifts induced more activation than backward shifts. Our results suggest that the differences in cerebellar activation patterns for different sizes and directions of post-saccadic errors could underlie the behavioral differences observed between various saccadic adaptation paradigms. In addition, the outcome argues for an extended range of cerebellar target areas in electrophysiological studies on saccadic eye movement control.
SOD1G93A Mutant Mice Develop a Neuroinflammation-Independent Dendropathy in Excitatory Neuronal Subsets of the Olfactory Bulb and Retina.
Journal of neuropathology and experimental neurology, 2017

Nonmotor neuron-related pathology is a feature of amyotrophic lateral sclerosis (ALS), both in patients and in animal models. There is emerging evidence that sensory systems (olfaction and vision) are affected in humans. Here, we asked whether such sensory neuropathology is recapitulated in the superoxide dismutase 1 (SOD1G93A) mouse model of ALS. Neuronal vacuolization in olfaction and vision pathways was assessed in tissue sections from presymptomatic and symptomatic disease stages, and compared to wild type. In both, the olfactory bulb and retina, vacuolization started around postnatal day 60, and vacuole sizes increased until disease end-stage. Notably, vacuolization was largely restricted to the external plexiform layer of the olfactory bulb and to the inner plexiform layer of the retina. In both layers, hSOD1-immunoreactive vacuoles localized to dendrites of excitatory neurons. Downstream olfaction and vision pathway fiber tracts and relay stations did not display obvious vacuolization. Finally, on a morphological level, there was no evidence for an activation of astrocytes and microglia in the 2 affected areas. Thus, we identified a new pathology hallmark in SOD1G93A ALS mice: a glutamatergic sensory neuron dendropathy restricted to olfactory bulb mitral cells and retinal ganglionic cells.
Short-interval intracortical inhibition in human primary motor cortex: A multi-locus transcranial magnetic stimulation study.
NeuroImage, 2019

Short-interval intracortical inhibition (SICI) has been studied with paired-pulse transcranial magnetic stimulation (TMS) by administering two pulses at a millisecond-scale interstimulus interval (ISI) to a single cortical target. It has, however, been difficult to study the interaction of nearby cortical targets with paired-pulse TMS. To overcome this limitation, we have developed a multi-locus TMS (mTMS) device, which allows controlling the stimulus location electronically. Here, we applied mTMS to study SICI in primary motor cortex with paired pulses targeted to adjacent locations, aiming to quantify the extent of the cortical region producing SICI in the location of a test stimulus. We varied the location and timing of the conditioning stimulus with respect to a test stimulus targeted to the cortical hotspot of the abductor pollicis brevis (APB) in order to study their effects on motor evoked potentials. We further applied a two-coil protocol with the conditioning stimulus given by an oval coil only to the surroundings of the APB hotspot, to which a subsequent test stimulus was administered with a figure-of-eight coil. The strongest SICI occurred at ISIs below 1 ms and at ISIs around 2.5 ms. These ISIs increased when the conditioning stimulus receded from the APB hotspot. Our two-coil paired-pulse TMS study suggests that SICI at ISIs of 0.5 and 2.5 ms originate from different mechanisms or neuronal elements.
Induction of angiopoietin-2 after spinal cord injury.
Neuroscience, 2012

Angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) have opposing effects on blood vessels, with Ang-2 being mainly induced during the endothelial barrier breakdown. It is known that spinal cord injury (SCI) induces lasting decreases in Ang-1 levels, underlying endothelial barrier disruption, but the expression of Ang-2 in spinal cord injury has not been studied. We characterized Ang-2 after SCI using a clinically relevant rat model of contusion SCI. We found that SCI induces marked and persistent upregulation of Ang-2 (up to 10 weeks after SCI), which does not reflect well-characterized temporal profile of the blood-spinal cord barrier (BSCB) breakdown after SCI, and thus suggests other role(s) for Ang-2 in injured spinal cords. Furthermore, we also found that higher Ang-2 levels were associated with more successful locomotor recovery after SCI, both in SCI rats with markedly better spontaneous motor recovery and in SCI rats receiving a neuroprotective pharmacological intervention (amiloride), suggesting a beneficial role for Ang-2 in injured spinal cords. Immunocytochemical analyses revealed that Ang-2 was not induced in endothelial cells, but in perivascular and non-vascular cells labeled with glial fibrillary acidic protein (GFAP) or with chondroitin sulfate proteoglycan (NG2). Therefore, it is unlikely that induction of Ang-2 contributes to vascular dysfunction underlying functional impairment after SCI, but rather that it contributes to the beneficial pro-angiogenic and/or gliogenic processes underlying recovery processes after SCI.
BDNF Val66Met polymorphism in patterns of neural activation in individuals with MDD and healthy controls.
Journal of affective disorders, 2015

Rs6265 single nucleotide polymorphism, which influences brain-derived neurotrophic factor (BDNF) levels in the cortical and subcortical brain structures, may result in distinguished patterns of neural activation during a major depressive disorder (MDD) episode. Valine homozygotes with high levels of BDNF and methionine carriers with lower levels of BDNF may present specific neural correlates of MDD. In our study we have tested differences in blood oxygen level dependant (BOLD) signal between individuals with MDD and healthy controls for both allelic variants.
No Evidence for Recent Selection at FOXP2 among Diverse Human Populations.
Cell, 2018

FOXP2, initially identified for its role in human speech, contains two nonsynonymous substitutions derived in the human lineage. Evidence for a recent selective sweep in Homo sapiens, however, is at odds with the presence of these substitutions in archaic hominins. Here, we comprehensively reanalyze FOXP2 in hundreds of globally distributed genomes to test for recent selection. We do not find evidence of recent positive or balancing selection at FOXP2. Instead, the original signal appears to have been due to sample composition. Our tests do identify an intronic region that is enriched for highly conserved sites that are polymorphic among humans, compatible with a loss of function in humans. This region is lowly expressed in relevant tissue types that were tested via RNA-seq in human prefrontal cortex and RT-PCR in immortalized human brain cells. Our results represent a substantial revision to the adaptive history of FOXP2, a gene regarded as vital to human evolution.
Synaptic vesicles transiently dock to refill release sites.
Nature neuroscience, 2020

Synaptic vesicles fuse with the plasma membrane to release neurotransmitter following an action potential, after which new vesicles must 'dock' to refill vacated release sites. To capture synaptic vesicle exocytosis at cultured mouse hippocampal synapses, we induced single action potentials by electrical field stimulation, then subjected neurons to high-pressure freezing to examine their morphology by electron microscopy. During synchronous release, multiple vesicles can fuse at a single active zone. Fusions during synchronous release are distributed throughout the active zone, whereas fusions during asynchronous release are biased toward the center of the active zone. After stimulation, the total number of docked vesicles across all synapses decreases by ~40%. Within 14 ms, new vesicles are recruited and fully replenish the docked pool, but this docking is transient and they either undock or fuse within 100 ms. These results demonstrate that the recruitment of synaptic vesicles to release sites is rapid and reversible.
Genetic insights into sporadic Parkinson's disease pathogenesis.
Current genomics, 2013

Intensive research over the last 15 years has led to the identification of several autosomal recessive and dominant genes that cause familial Parkinson's disease (PD). Importantly, the functional characterization of these genes has shed considerable insights into the molecular mechanisms underlying the etiology and pathogenesis of PD. Collectively; these studies implicate aberrant protein and mitochondrial homeostasis as key contributors to the development of PD, with oxidative stress likely acting as an important nexus between the two pathogenic events. Interestingly, recent genome-wide association studies (GWAS) have revealed variations in at least two of the identified familial PD genes (i.e. α-synuclein and LRRK2) as significant risk factors for the development of sporadic PD. At the same time, the studies also uncovered variability in novel alleles that is associated with increased risk for the disease. Additionally, in-silico meta-analyses of GWAS data have allowed major steps into the investigation of the roles of gene-gene and gene-environment interactions in sporadic PD. The emergent picture from the progress made thus far is that the etiology of sporadic PD is multi-factorial and presumably involves a complex interplay between a multitude of gene networks and the environment. Nonetheless, the biochemical pathways underlying familial and sporadic forms of PD are likely to be shared.
Behavioural state-specific neurons in the mouse medulla involved in sleep-wake switching.
The European journal of neuroscience, 2018

The medullary reticular formation (RF) is involved in the maintenance of several vital physiological functions and level of vigilance. In this study, in nonanesthetised, head-fixed mice, I examined the role of medullary RF neurons in the control of sleep-wake states, that is, wakefulness (W), slow-wave sleep (SWS) and paradoxical (or rapid eye movement) sleep (PS). I showed, for the first time, that the mouse medullary RF contains presumed SWS-promoting, SWS-on neurons that remain silent during W, display a sharp increase in discharge rate at sleep onset, and discharge tonically and selectively during SWS. In addition, I showed the presence in the medullary RF of both PS-on and PS-off neurons, which, respectively, commence discharging or cease firing selectively just prior to, and during, PS. PS-off neurons were located in the raphe nuclei and ventral medulla, while PS-on neurons were found in both the lateral part of the ventral gigantocellular reticular nucleus and the raphe nuclei, as were SWS-on neurons. PS-off and SWS-on neurons appear to play an important role in both the W-SWS and SWS-PS switches, while PS-on and PS-off neurons play an important role in the PS-W switch. The present findings on the trends in spike activity at the transitions from SWS to PS and from PS to W are in line with the reciprocal interaction hypothesis according to which PS occurs as a result of the cessation of discharge of PS-off neurons, while PS ends as a result of the start of discharge of PS-off neurons.
Bisphenol S modulates concentrations of bisphenol A and oestradiol in female and male mice.
Xenobiotica; the fate of foreign compounds in biological systems, 2019

Concern over endocrine-disrupting actions of bisphenol A (BPA) has prompted some manufacturers to remove it from consumer products. Among the chemical replacements in "BPA-free" products are other bisphenol analogues, such as bisphenol S (BPS). Given evidence that BPA and BPS possess similar oestrogenic activity, their capacity to interact and disrupt oestrogen homeostasis should be examined. We investigated whether BPS can modulate concentrations of
Reexamination of diathesis stress and neurotoxic stress theories: A qualitative review of pre-trauma neurobiology in relation to posttraumatic stress symptoms.
International journal of methods in psychiatric research, 2021

Associations of neurobiological differences with posttraumatic stress disorder (PTSD) have generated interest in their temporal relation. Support has been voiced for the neurotoxic stress theory (NST) in which neurobiological differences develop following exposure and PTSD development. In contrast, the diathesis stress theory (DST) posits that neurobiological differences existed prior to exposure and may be vulnerability factors for PTSD. Studies in the first wave of neurobiological PTSD research were all cross sectional, but a second wave of research followed which used prospective repeated-measures designs that measured neurobiology prior to trauma exposure experiences, allowing greater causal inference.
Capsaicin-sensitive primary sensory neurons in the mouse express N-Acyl phosphatidylethanolamine phospholipase D.
Neuroscience, 2009

Our previous finding, that the capsaicin- and KCl-induced Ca(2+)-dependent production of the intra- and intercellular signaling molecule N-arachidonoyl ethanolamine (anandamide) in cultured primary sensory neurons could be abolished and reduced by approximately 2/3 by capsaicin-induced degeneration of capsaicin-sensitive neurons, respectively suggests that a major sub-population of capsaicin-sensitive cells together with a group of non-capsaicin-sensitive cells should express enzymes involved in Ca(2+)-dependent anandamide synthesis. N-acyl phosphotidylethanolamine phospholipase D (NAPE-PLD) is known to be involved in Ca(2+)-dependent anandamide production. Hence, here, we used reverse transcriptase and quantitative real time polymerase chain reaction to study NAPE-PLD expression in dorsal root ganglia and to clarify the sub-population of cells expressing this enzyme. Cultures prepared from mouse dorsal root ganglia were grown either in the absence or presence of the neurotoxin, capsaicin (10 muM) overnight. We report, that NAPE-PLD is expressed both in dorsal root ganglia and cultures prepared from dorsal root ganglia and grown in the absence of capsaicin. Furthermore, we also report that capsaicin application downregulates the expression of NAPE-PLD as well as the capsaicin receptor, transient receptor potential vanilloid type 1 ion channel, by about 70% in the cultures prepared from dorsal root ganglia. These findings indicate that a major sub-population of capsaicin-sensitive primary sensory neurons expresses NAPE-PLD, and suggest that NAPE-PLD is expressed predominantly by capsaicin-sensitive neurons in dorsal root ganglia. These data also suggest that NAPE-PLD might be a target to control the activity and excitability of a major sub-population of nociceptive primary sensory neurons.
Pre-diagnostic vitamin D concentrations and cancer risks in older individuals: an analysis of cohorts participating in the CHANCES consortium.
European journal of epidemiology, 2016

The associations of circulating 25-hydroxyvitamin D [25(OH)D] concentrations with total and site-specific cancer incidence have been examined in several epidemiological studies with overall inconclusive findings. Very little is known about the association of vitamin D with cancer incidence in older populations. We assessed the association of pre-diagnostic serum 25(OH)D levels with incidence of all cancers combined and incidence of lung, colorectal, breast, prostate and lymphoid malignancies among older adults. Pre-diagnostic 25(OH)D concentrations and cancer incidence were available in total for 15,486 older adults (mean age 63, range 50-84 years) participating in two cohort studies: ESTHER (Germany) and TROMSØ (Norway); and a subset of previously published nested-case control data from a another cohort study: EPIC-Elderly (Greece, Denmark, Netherlands, Spain and Sweden) from the CHANCES consortium on health and aging. Cox proportional hazards or logistic regression were used to derive multivariable adjusted hazard and odds ratios, respectively, and their 95% confidence intervals across 25(OH)D categories. Meta-analyses with random effects models were used to pool study-specific risk estimates. Overall, lower 25(OH)D concentrations were not significantly associated with increased incidence of most of the cancers assessed. However, there was some evidence of increased breast cancer and decreased lymphoma risk with higher 25(OH)D concentrations. Our meta-analyses with individual participant data from three large European population-based cohort studies provide at best limited support for the hypothesis that vitamin D may have a major role in cancer development and prevention among European older adults.
The extracellular HDAC6 ZnF UBP domain modulates the actin network and post-translational modifications of Tau.
Cell communication and signaling : CCS, 2021

Microtubule-associated protein Tau undergoes aggregation in Alzheimer`s disease (AD) and a group of other related diseases collectively known as Tauopathies. In AD, Tau forms aggregates, which are deposited intracellularly as neurofibrillary tangles. Histone deacetylase-6 (HDAC6) plays an important role in aggresome formation, where it recruits polyubiquitinated aggregates to the motor protein dynein.
An illustration of collaborative care with a focus on the role of fathers in Maudsley Anorexia Nervosa Treatment for Adults (MANTRA).
Journal of clinical psychology, 2019

The aim of this case study is to illustrate the importance of collaborative care as part of Maudsley Anorexia Nervosa Treatment for Adults (MANTRA). Mothers are often at the foreground of providing support within the family. However, fathers have the potential to play a profound role. In this paper, we describe a patient with anorexia nervosa treated with the MANTRA. The formulation of this case included autistic spectrum traits in both the father and daughter leading to social isolation. We describe how the family members were engaged into treatment and how paternal support was used to promote social connection and an improved quality of life in the daughter. Some details of the case have been altered to maintain confidentiality.
A Neural Representation of Naturalistic Motion-Guided Behavior in the Zebrafish Brain.
Current biology : CB, 2020

All animals must transform ambiguous sensory data into successful behavior. This requires sensory representations that accurately reflect the statistics of natural stimuli and behavior. Multiple studies show that visual motion processing is tuned for accuracy under naturalistic conditions, but the sensorimotor circuits extracting these cues and implementing motion-guided behavior remain unclear. Here we show that the larval zebrafish retina extracts a diversity of naturalistic motion cues, and the retinorecipient pretectum organizes these cues around the elements of behavior. We find that higher-order motion stimuli, gliders, induce optomotor behavior matching expectations from natural scene analyses. We then image activity of retinal ganglion cell terminals and pretectal neurons. The retina exhibits direction-selective responses across glider stimuli, and anatomically clustered pretectal neurons respond with magnitudes matching behavior. Peripheral computations thus reflect natural input statistics, whereas central brain activity precisely codes information needed for behavior. This general principle could organize sensorimotor transformations across animal species.