rudyvdbrink/CitationDatabase huggingface dataset:
Evaluation of cholesterol metabolism in cerebrotendinous xanthomatosis.
Journal of inherited metabolic disease, 2016

Cerebrotendinous xanthomatosis (CTX) is a treatable bile acid disorder caused by mutations of CYP27A1. The pathogenesis of neurological damage has not been completely explained. Oral chenodeoxycholic acid (CDCA) can lead to clinical stabilization, but in a subgroup of patients the disease progresses despite treatment. In the present study, we aimed at clarifying cholesterol metabolism abnormalities and their response to CDCA treatment, in order to identify reliable diagnostic and prognostic markers and understand if differences exist between stable patients and those with neurological progression.
Computational modeling of resting-state activity demonstrates markers of normalcy in children with prenatal or perinatal stroke.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015

Children who sustain a prenatal or perinatal brain injury in the form of a stroke develop remarkably normal cognitive functions in certain areas, with a particular strength in language skills. A dominant explanation for this is that brain regions from the contralesional hemisphere "take over" their functions, whereas the damaged areas and other ipsilesional regions play much less of a role. However, it is difficult to tease apart whether changes in neural activity after early brain injury are due to damage caused by the lesion or by processes related to postinjury reorganization. We sought to differentiate between these two causes by investigating the functional connectivity (FC) of brain areas during the resting state in human children with early brain injury using a computational model. We simulated a large-scale network consisting of realistic models of local brain areas coupled through anatomical connectivity information of healthy and injured participants. We then compared the resulting simulated FC values of healthy and injured participants with the empirical ones. We found that the empirical connectivity values, especially of the damaged areas, correlated better with simulated values of a healthy brain than those of an injured brain. This result indicates that the structural damage caused by an early brain injury is unlikely to have an adverse and sustained impact on the functional connections, albeit during the resting state, of damaged areas. Therefore, these areas could continue to play a role in the development of near-normal function in certain domains such as language in these children.
Prenatal EDCs Impair Mate and Odor Preference and Activation of the VMN in Male and Female Rats.
Endocrinology, 2020

Environmental endocrine-disrupting chemicals (EDCs) disrupt hormone-dependent biological processes. We examined how prenatal exposure to EDCs act in a sex-specific manner to disrupt social and olfactory behaviors in adulthood and underlying neurobiological mechanisms. Pregnant rat dams were injected daily from embryonic day 8 to 18 with 1 mg/kg Aroclor 1221 (A1221), 1 mg/kg vinclozolin, or the vehicle (6% DMSO in sesame oil). A1221 is a mixture of polychlorinated biphenyls (weakly estrogenic) while vinclozolin is a fungicide (anti-androgenic). Adult male offspring exposed to A1221 or vinclozolin, and females exposed to A1221, had impaired mate preference behavior when given a choice between 2 opposite-sex rats that differed by hormone status. A similar pattern of impairment was observed in an odor preference test for urine-soaked filter paper from the same rat groups. A habituation/dishabituation test revealed that all rats had normal odor discrimination ability. Because of the importance of the ventrolateral portion of the ventromedial nucleus (VMNvl) in mate choice, expression of the immediate early gene product Fos was measured, along with its co-expression in estrogen receptor alpha (ERα) cells. A1221 females with impaired mate and odor preference behavior also had increased neuronal activation in the VMNvl, although not specific to ERα-expressing neurons. Interestingly, males exposed to EDCs had normal Fos expression in this region, suggesting that other neurons and/or brain regions mediate these effects. The high conservation of hormonal, olfactory, and behavioral traits necessary for reproductive success means that EDC contamination and its ability to alter these traits has widespread effects on wildlife and humans.
Probing axons using multi-compartmental diffusion in multiple sclerosis.
Annals of clinical and translational neurology, 2019

The diffusion-based spherical mean technique (SMT) provides a novel model to relate multi-b-value diffusion magnetic resonance imaging (MRI) data to features of tissue microstructure. We propose the first clinical application of SMT to image the brain of patients with multiple sclerosis (MS) and investigate clinical feasibility and translation.
PKR-like endoplasmic reticulum kinase (PERK) activation following brain ischemia is independent of unfolded nascent proteins.
Neuroscience, 2010

Transient global brain ischemia results in an immediate inhibition of protein translation upon reperfusion. During early brain reperfusion protein synthesis is inhibited by alpha subunit of eukaryotic initiation factor 2 (eIF2alpha) phosphorylation by the PKR-like endoplasmic reticulum kinase (PERK). Normally, PERK is held in an inactive, monomeric state by the binding of the endoplasmic reticulum (ER) chaperone GRP78 to the lumenal end of PERK. The prevailing view is that ER stress leads to the accumulation of unfolded proteins in the ER lumen. GRP78 dissociates from PERK to bind these accumulated unfolded proteins, leading to PERK activation, phosphorylation of eIF2alpha, and inhibition of translation. To determine if an increase in unfolded nascent proteins following transient brain ischemia contributes to PERK activation, protein synthesis was blocked by intracerebral injection of anisomycin prior to induction of ischemia. Anisomycin inhibited protein synthesis by over 99% and reduced newly synthesized proteins in the ER to approximately 20% of controls. With an ER nearly devoid of newly synthesized proteins, PERK was still activated and was able to phosphorylate eIF2alpha in CA1 neurons during reperfusion. These data strongly argue that PERK activation is independent of the large increase in unfolded nascent proteins within the ER following transient global brain ischemia.
Quantitative and fiber-selective evaluation of pain and sensory dysfunction in patients with Parkinson's disease.
Parkinsonism & related disorders, 2015

Pain and sensory disturbances affect many patients with Parkinson's disease (PD). The present study aimed to evaluate the pain and sensory sensitivity of each class of afferent fibers in PD patients and determine the effects of dopaminergic therapy on pain and sensory sensitivity.
Sleep active cortical neurons expressing neuronal nitric oxide synthase are active after both acute sleep deprivation and chronic sleep restriction.
Neuroscience, 2013

Non-rapid eye movement (NREM) sleep electroencephalographic (EEG) delta power (~0.5-4 Hz), also known as slow wave activity (SWA), is typically enhanced after acute sleep deprivation (SD) but not after chronic sleep restriction (CSR). Recently, sleep-active cortical neurons expressing neuronal nitric oxide synthase (nNOS) were identified and associated with enhanced SWA after short acute bouts of SD (i.e., 6h). However, the relationship between cortical nNOS neuronal activity and SWA during CSR is unknown. We compared the activity of cortical neurons expressing nNOS (via c-Fos and nNOS immuno-reactivity, respectively) and sleep in rats in three conditions: (1) after 18-h of acute SD; (2) after five consecutive days of sleep restriction (SR) (18-h SD per day with 6h ad libitum sleep opportunity per day); (3) and time-of-day matched ad libitum sleep controls. Cortical nNOS neuronal activity was enhanced during sleep after both 18-h SD and 5 days of SR treatments compared to control treatments. SWA and NREM sleep delta energy (the product of NREM sleep duration and SWA) were positively correlated with enhanced cortical nNOS neuronal activity after 18-h SD but not 5days of SR. That neurons expressing nNOS were active after longer amounts of acute SD (18h vs. 6h reported in the literature) and were correlated with SWA further suggest that these cells might regulate SWA. However, since these neurons were active after CSR when SWA was not enhanced, these findings suggest that mechanisms downstream of their activation are altered during CSR.
Role of neurokinin receptors and ionic mechanisms within the respiratory network of the lamprey.
Neuroscience, 2010

We have suggested that in the lamprey, a medullary region called the paratrigeminal respiratory group (pTRG), is essential for respiratory rhythm generation and could correspond to the pre-Bötzinger complex (pre-BötC), the hypothesized kernel of the inspiratory rhythm-generating network in mammals. The present study was performed on in vitro brainstem preparations of adult lampreys to investigate whether some functional characteristics of the respiratory network are retained throughout evolution and to get further insights into the recent debated hypotheses on respiratory rhythmogenesis in mammals, such as for instance the "group-pacemaker" hypothesis. Thus, we tried to ascertain the presence and role of neurokinins (NKs) and burst-generating ion currents, such as the persistent Na(+) current (I(NaP)) and the Ca(2+)-activated non-specific cation current (I(CAN)), described in the pre-Bötzinger complex. Respiratory activity was monitored as vagal motor output. Substance P (SP) as well as NK1, NK2 and NK3 receptor agonists (400-800 nM) applied to the bath induced marked increases in respiratory frequency. Microinjections (0.5-1 nl) of SP as well as the other NK receptor agonists (1 microM) into the pTRG increased the frequency and amplitude of vagal bursts. Riluzole (RIL) and flufenamic acid (FFA) were used to block I(NaP) and I(CAN), respectively. Bath application of either RIL or FFA (20-50 microM) depressed, but did not suppress respiratory activity. Coapplication of RIL and FFA at 50 microM abolished the respiratory rhythm that, however, was restarted by SP microinjected into the pTRG. The results show that NKs may have a modulatory role in the lamprey respiratory network through an action on the pTRG and that I(NaP) and I(CAN) may contribute to vagal burst generation. We suggest that the "group-pacemaker" hypothesis is tenable for the lamprey respiratory rhythm generation since respiratory activity is abolished by blocking both I(NaP) and I(CAN), but is restored by enhancing network excitability.
Diagnostic value of serum biomarkers FGF21 and GDF15 compared to muscle sample in mitochondrial disease.
Journal of inherited metabolic disease, 2021

The aim of this study was to compare the value of serum biomarkers, fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15), with histological analysis of muscle in the diagnosis of mitochondrial disease. We collected 194 serum samples from patients with a suspected or known mitochondrial disease. Biomarkers were analyzed blinded using enzyme-labeled immunosorbent assay. Clinical data were collected using a structured questionnaire. Only 39% of patients with genetically verified mitochondrial disease had mitochondrial pathology in their muscle histology. In contrast, biomarkers were elevated in 62% of patients with genetically verified mitochondrial disease. Those with both biomarkers elevated had a muscle manifesting disorder and a defect affecting mitochondrial DNA expression. If at least one of the biomarkers was induced and the patient had a myopathic disease, a mitochondrial DNA expression disease was the cause with 94% probability. Among patients with biomarker analysis and muscle biopsy taken <12 months apart, a mitochondrial disorder would have been identified in 70% with analysis of FGF21 and GDF15 compared to 50% of patients whom could have been identified with muscle biopsy alone. Muscle findings were nondiagnostic in 72% (children) and 45% (adults). Induction of FGF21 and GDF15 suggest a mitochondrial etiology as an underlying cause of a muscle manifesting disease. Normal biomarker values do not, however, rule out a mitochondrial disorder, especially if the disease does not manifest in muscle. We suggest that FGF21 and GDF15 together should be first-line diagnostic investigations in mitochondrial disease complementing muscle biopsy.
Multiple extinction contexts modulate the neural correlates of context-dependent extinction learning and retrieval.
Neurobiology of learning and memory, 2020

Exposure therapy is a successful treatment for patients with anxiety and fear-related disorders. Extinction of conditioned fear comprises one important mechanism underlying the effects of exposure therapy. Yet, relapses frequently occur in the long-term, probably related to difficulties in generalizing the extinction of conditioned fear to new contexts, leading to renewal of conditioned fear. Extinction training in multiple extinction contexts depicts a promising opportunity to reduce this renewal of conditioned fear. However, the underlying neural correlates are unknown yet. In this functional magnetic resonance imaging study, 49 healthy men participated in a fear conditioning paradigm with fear acquisition training in context A on a first day, extinction training in a single context (B1) or in four different contexts (B1-B4) one day later, and fear and extinction recall and reinstatement in context B1 and a novel context C on a third day one week later. Multiple extinction contexts led to a stronger differential activation decrease in the hippocampus during extinction learning compared to a single extinction context. One week later, the multiple context group compared with the single context group showed reduced differential amygdala activation during fear renewal in the novel context C compared with the extinction context B1. Furthermore, multiple extinction contexts diminished amygdala activation during a subsequent reinstatement test in context B1. However, there were no significant differences in differential conditioned SCRs. These results indicate that the use of multiple extinction contexts during extinction training leads to reduced conditioned responses in the amygdala-hippocampus complex.
In vivo biased agonism at 5-HT
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2018

In neuropharmacology, the recent concept of 'biased agonism' denotes the capacity of certain agonists to target-specific intracellular pathways of a given receptor in specific brain areas. In the context of serotonin pharmacotherapy, 5-HT
Small GTPases of the Ras superfamily and glycogen phosphorylase regulation in T cells.
Small GTPases, 2021

Small GTPases, together with their regulatory and effector molecules, are key intermediaries in the complex signalling pathways that control almost all cellular processes, working as molecular switches to transduce extracellular cues into cellular responses that drive vital functions, such as intracellular transport, biomolecule synthesis, gene activation and cell survival. How all of these networks are linked to metabolic pathways is a subject of intensive study. Because any response to cellular action requires some form of energy input, elucidating how cells coordinate the signals that lead to a tangible response involving metabolism is central to understand cellular activities. In this review, we summarize recent advances in our understanding of the molecular basis of the crosstalk between small GTPases of the Ras superfamily, specifically Rac1 and Ras/Rap1, and glycogen phosphorylase in T lymphocytes.
Caloric restriction provided after global ischemia does not reduce hippocampal cornu ammonis injury or improve functional recovery.
Neuroscience, 2010

Since caloric restriction (CR) can modify multiple pathways central to the ischemic cascade and enhance neuroplasticity mechanisms, we hypothesized that CR should exert protective effects following brain ischemia. Previous studies have suggested benefit when CR was administered prior to ischemia. We investigated whether prolonged CR beginning after global ischemia would result in lasting protection as assessed by performance in the open field, as a measure of functional outcome, and hippocampal CA1 neuronal counts. Adult, male Mongolian gerbils were subjected to 5 min bilateral carotid artery occlusion (ISCH) or sham surgery (SHAM) with tympanic temperature maintained at 36.5+/-0.2 degrees C during the intra-ischemic period. After screening out gerbils with incomplete ischemia, each of the two surgical groups were randomly assigned to control diet (CON) or 30% CR for the duration of the study (60 d). Gerbils were tested in the open field on d3, 7, 10, 30 and 60. ISCH-CON animals showed a significantly higher level of activity in the open field (impaired habituation) compared to SHAM-CON gerbils on all test days (P<0.001). Open field activity was significantly lower in the ISCH-CR group than in ISCH-CON gerbils only on d7 (P=0.024). Open field activity of the SHAM-CR gerbils showed a trend to increase relative to that of SHAM-CON gerbils during the last 30 d of the study (P=0.055 on d60), raising the question of suitability of the open field test for long-term studies of CR and ischemia. Brain sections obtained at d60 were stained with hematoxylin and eosin. Hippocampal CA1 neuron counts were significantly reduced by ischemia (P<0.001), and there was no sparing effect of CR. Our findings suggest that prolonged 30% CR administered beginning after global ischemia cannot diminish brain injury or enhance long-term recovery.
Long-term impairment of behavioral recovery from cortical damage can be produced by short-term GABA-agonist infusion into adjacent cortex.
Restorative neurology and neuroscience, 1990

Diazepam and other GABA-related agents can prevent or delay recovery from an otherwise short-term somatosensory asymmetry caused by unilateral cortical lesions. Postrecovery treatment does not affect behavior. One possible contributive site of action for these agents is remaining cortical tissue. In the present study, following unilateral anteromedial cortex (AMC) lesions or sham operations, the GABA agonist muscimol or saline was infused once a day for 7 days into the adjacent sensorimotor cortex (SMC) or, as a control, into the more remote occipital cortex (OC) of the ipsilateral hemisphere. Each day the animals were given somatosensory and motor coordination tests at 21 h postinfusion. The SMC-muscimol regimen, but not the SMC-saline or OC-muscimol, retarded recovery from somatosensory asymmetry. The disruptive effect on recovery was enduring, greatly outlasting the week of exposure to muscimol. In sham-operated animals, SMC-muscimoI did not yield a chronic effect on behavior, although during the first hour after each infusion, in which the muscimol presumably was still present in the SMC, somatosensory asymmetry could be observed. Although the AMC lesion created a vulnerability to muscimol in the SMC, no detectable difference in the extent of cortical damage in this group could account for the prolongation of behavioral asymmetry. SMC-muscimol (but not SMC-saline) led to atrophy of SMC projection areas in the ipsilateral thalamus. However, in sham-operated animals, SMC-muscimol did not affect thalamic size. These behavioral and anatomical data suggest that systemically delivered GABAergic drugs might interfere with restoration of function after AMC lesions in part by adversely influencing events in the SMC.
Effects of Korean red ginseng extracts on neural tube defects and impairment of social interaction induced by prenatal exposure to valproic acid.
Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, 2013

Ginseng is one of the most widely used medicinal plants, which belongs to the genus Panax. Compared to uncured white ginseng, red ginseng has been generally regarded to produce superior pharmacological effects with lesser side/adverse effects, which made it popular in a variety of formulation from tea to oriental medicine. Using the prenatal valproic acid (VPA)-injection model of autism spectrum disorder (ASD) in rats, which produces social impairrment and altered seizure susceptibility as in human ASD patients as well as mild neural tube defects like crooked tail phenotype, we examined whether chronic administration of red ginseng extract may rescue the social impairment and crooked tail phenotype in prenatally VPA-exposed rat offspring. VPA-induced impairment in social interactions tested using sociability and social preference paradigms as well as crooked tail phenotypes were significantly improved by administration of Korean red ginseng (KRG) in a dose dependent manner. Rat offspring prenatally exposed to VPA showed higher sensitivity to electric shock seizure and increased locomotor activity in open-field test. KRG treatment reversed abnormal locomotor activity and sensitivity to electric shock to control level. These results suggest that KRG may modulate neurobehavioral and structural organization of nervous system adversely affected by prenatal exposure to VPA.
Exploring biased attention towards body-related stimuli and its relationship with body awareness.
Scientific reports, 2017

Stimuli of great social relevance exogenously capture attention. Here we explored the impact of body-related stimuli on endogenous attention. Additionally, we investigate the influence of internal states on biased attention towards this class of stimuli. Participants were presented with a body, face, or chair cue to hold in memory (Memory task) or to merely attend (Priming task) and, subsequently, they were asked to find a circle in an unrelated visual search task. In the valid condition, the circle was flanked by the cue. In the invalid condition, the pre-cued picture re-appeared flanking the distracter. In the neutral condition, the cue item did not re-appear in the search display. We found that although bodies and faces benefited from a general faster visual processing compared to chairs, holding them in memory did not produce any additional advantage on attention compared to when they are merely attended. Furthermore, face cues generated larger orienting effect compared to body and chairs cues in both Memory and Priming task. Importantly, results showed that individual sensitivity to internal bodily responses predicted the magnitude of the memory-based orienting of attention to bodies, shedding new light on the relationship between body awareness and visuo-spatial attention.
The past, present and future of social neuroscience: a European perspective.
NeuroImage, 2012

This review provides an overview of the field of social neuroscience from a European perspective and focuses mainly on outlining research topics which originated in European laboratories. After a brief historical synopsis of the emergence of this young field, the most relevant findings related to the investigation of the neural networks underlying our capacity to understand the minds of others are summarized. More specifically, three routes of social cognition are distinguished: (1) our capacity to mentalize, or to infer intentions and beliefs of others, (2) our capacity to mimic and understand other's motor actions, and (3) our capacity to empathize, or to share and understand the feelings of others. More recent studies focusing on social emotions such as love, compassion, revenge or our sense of fairness will be discussed linking the field of social neuroscience to the even younger field of neuroeconomics, with the focus on the study of human social interactions using game theoretical paradigms. Finally, the use of a multi-method and multi-disciplinary research approach combining genetic, pharmacological, computational and developmental aspects is advocated and future directions for the study of interactive minds are discussed.