rudyvdbrink/CitationDatabase huggingface dataset:
Neuropeptide S reduces mouse aggressiveness in the resident/intruder test through selective activation of the neuropeptide S receptor.
Neuropharmacology, 2015

Neuropeptide S (NPS) regulates various biological functions by selectively activating the NPS receptor (NPSR). In particular NPS evokes robust anxiolytic-like effects in rodents together with a stimulant and arousal promoting action. The aim of the study was to investigate the effects of NPS on the aggressiveness of mice subjected to the resident/intruder test. Moreover the putative role played by the endogenous NPS/NPSR system in regulating mice aggressiveness was investigating using mice lacking the NPSR receptor (NPSR(-/-)) and the NPSR selective antagonists [(t)Bu-D-Gly(5)]NPS and SHA 68. NPS (0.01-1 nmol, icv) reduced, in a dose dependent manner, both the time that resident mice spent attacking the intruder mice and their number of attacks, producing pharmacological effects similar to those elicited by the standard anti-aggressive drug valproate (300 mg/kg, ip). This NPS effect was evident in NPSR wild type (NPSR(+/+)) mice but completely disappeared in NPSR(-/-) mice. Moreover, NPSR(-/-) mice displayed a significantly higher time spent attacking than NPSR(+/+) mice. [(t)Bu-D-Gly(5)]NPS (10 nmol, icv) did not change the behavior of mice in the resident/intruder test but completely counteracted NPS effects. SHA 68 (50 mg/kg, ip) was inactive per se and against NPS. In conclusion, this study demonstrated that NPS produces anti-aggressive effects in mice through the selective activation of NPSR and that the endogenous NPS/NPSR system can exert a role in the control of aggressiveness levels under the present experimental conditions.
Progress and challenges in probing the human brain.
Nature, 2015

Perhaps one of the greatest scientific challenges is to understand the human brain. Here we review current methods in human neuroscience, highlighting the ways that they have been used to study the neural bases of the human mind. We begin with a consideration of different levels of description relevant to human neuroscience, from molecules to large-scale networks, and then review the methods that probe these levels and the ability of these methods to test hypotheses about causal mechanisms. Functional MRI is considered in particular detail, as it has been responsible for much of the recent growth of human neuroscience research. We briefly review its inferential strengths and weaknesses and present examples of new analytic approaches that allow inferences beyond simple localization of psychological processes. Finally, we review the prospects for real-world applications and new scientific challenges for human neuroscience.
The central circadian timing system.
Current opinion in neurobiology, 2013

It has been known since the 1970s that the suprachiasmatic nucleus (SCN) is the brain's main biological clock, and since the 1990s that it uses a genetic clock based on transcriptional-translational loops to tell time. However, the recent demonstration that many other cells in the brain and the body also make use of the same genetic clock raises the question of how the SCN synchronizes all of the other clocks to arrive at a coherent circadian profile of physiology and behavior. In this review, we re-examine the evidence that the SCN clock is necessary for bringing order to the body's biological rhythms, and the circuitry of the circadian timing system by which it accomplishes this goal. Finally, we review the evidence that under conditions of restricted food availability, other clocks may be able to take over from the SCN to determine rhythms of behavior and physiology.
Concurrent Risperidone Administration Attenuates the Development of Locomotor Sensitization Following Sub-Chronic Phencyclidine in Rats.
Pharmacopsychiatry, 2016

In schizophrenia early treatment may prevent disorder onset, or at least minimize its impact, suggesting possible neuroprotective properties of antipsychotics. The present study investigates the effects of chronic treatment with the atypical antipsychotic, risperidone, on locomotor sensitization in the subchronic phencyclidine-treated rat.
A longitudinal study of cortical grey matter lesion subtypes in relapse-onset multiple sclerosis.
Journal of neurology, neurosurgery, and psychiatry, 2016

Cortical grey matter (GM) lesions are common in multiple sclerosis (MS), but little is known about their temporal evolution. We investigated this in people with relapsing-remitting (RR) and secondary progressive (SP) MS.
Mechanosensitive TRPC1 channels promote calpain proteolysis of talin to regulate spinal axon outgrowth.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013

Intracellular Ca(2+) signals control the development and regeneration of spinal axons downstream of chemical guidance cues, but little is known about the roles of mechanical cues in axon guidance. Here we show that transient receptor potential canonical 1 (TRPC1) subunits assemble mechanosensitive (MS) channels on Xenopus neuronal growth cones that regulate the extension and direction of axon outgrowth on rigid, but not compliant, substrata. Reducing expression of TRPC1 by antisense morpholinos inhibits the effects of MS channel blockers on axon outgrowth and local Ca(2+) transients. Ca(2+) influx through MS TRPC1 activates the protease calpain, which cleaves the integrin adaptor protein talin to reduce Src-dependent axon outgrowth, likely through altered adhesion turnover. We found that talin accumulates at the tips of dynamic filopodia, which is lost upon cleavage of talin by active calpain. This pathway may also be important in axon guidance decisions since asymmetric inhibition of MS TRPC1 is sufficient to induce growth cone turning. Together our results suggest that Ca(2+) influx through MS TRPC1 on filopodia activates calpain to control growth cone turning during development.
Severity of nicotine dependence moderates performance on perceptual-motor tests of attention.
Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco, 2008

Acute abstinence from cigarette smoking by nicotine-dependent smokers has been linked with cognitive deficits, but the role of nicotine dependence per se in these effects is not known. We therefore tested the relationships of nicotine dependence and smoking history with performance in perceptual-motor, timed tests of attention. Nicotine-dependent smokers (n = 37) and nonsmokers (n = 48), 18-55 years old, took both the d2 Test of Attention and the Digit Symbol Test on each of 2 test days. For smokers, testing on one day began after ad libitum smoking (<45 min since last cigarette); and on the other day, it began after overnight abstinence (>13 hr since last cigarette). On each test day, there were two test blocks with an intervening break, when only the smokers each smoked one cigarette. There were no significant effects of abstinence or of smoking one cigarette on the performance of smokers; however, across conditions, the smokers' performance on both tests correlated negatively with severity of nicotine dependence but not lifetime cigarette consumption or cigarette craving. Smokers with high nicotine dependence performed more slowly on both tests than less dependent smokers or nonsmokers. The findings suggest that severity of nicotine dependence and slowness in perceptual-motor tasks of attention share an underlying basis.
Nanoparticle/siRNA-based therapy strategies in glioma: which nanoparticles, which siRNAs?
Nanomedicine (London, England), 2018

Nanomedicines allow for the delivery of small interfering RNAs (siRNAs) that are otherwise barely suitable as therapeutics for inducing RNA interference (RNAi). In preclinical studies on siRNA-based glioma treatment in vivo, various groups of nanoparticle systems, routes of administration and target genes have been explored. Targeted delivery by functionalization of nanoparticles with a ligand for crossing the blood-brain barrier and/or for enhanced target cell transfection has been described as well. Focusing on nanoparticle developments in the last approximately 10 years, this review article gives a comprehensive overview of nanoparticle systems for siRNA delivery into glioma and of preclinical in vivo studies. Furthermore, it discusses various target genes and highlights promising strategies with regard to target gene selection and combination therapies.
Naloxone in ultralow concentration restores endomorphin-1-evoked Ca²⁺ signaling in lipopolysaccharide pretreated astrocytes.
Neuroscience, 2012

Long-term pain is a disabling condition that affects thousands of people. Pain may be sustained for a long time even after the physiological trigger has resolved. Possible mechanisms for this phenomenon include low-grade inflammation in the CNS. Astrocytes respond to inflammatory stimuli and may play an important role as modulators of the inflammatory response in the nervous system. This study aimed first to assess how astrocytes in a primary culture behave when exposed to the endogenous μ-opioid receptor agonist endomorphin-1 (EM-1), in a concentration-dependent manner, concerning intracellular Ca²⁺ responses. EM-1 stimulated the μ-opioid receptor from 10⁻¹⁵ M up to 10⁻⁴ M with increasing intensity, usually reflected as one peak at low concentrations and two peaks at higher concentrations. Naloxone, pertussis toxin (PTX), or the μ-opioid receptor antagonists CTOP did not totally block the EM-1-evoked Ca²⁺ responses. However, a combination of ultralow concentration naloxone (10⁻¹² M) and PTX (100 ng/ml) totally blocked the EM-1-evoked Ca²⁺ responses. This suggests that ultralow (picomolar) concentrations of naloxone should block the μ-opioid receptor coupled G(s) protein, and that PTX should block the μ-opioid receptor coupled G(i/o) protein. The second aim was to investigate exposure of astrocytes with the inflammatory agent lipopolysaccharide (LPS). After 4 h of LPS incubation, the EM-1-evoked Ca²⁺ transients were attenuated, and after 24 h of LPS incubation, the EM-1-evoked Ca²⁺ transients were oscillated. To restore the EM-1-evoked Ca²⁺ transients, naloxone was assessed as a proposed anti-inflammatory substance. In ultralow picomolar concentration, naloxone demonstrated the ability to restore the Ca²⁺ transients.
A Review of the Neuropsychological Dimensions of Tourette Syndrome.
Brain sciences, 2017

Neurocognitive functioning in Tourette syndrome (TS) has been the subject of intensive research in the past 30 years. A variety of impairments, presumably related to frontal and frontostriatal dysfunctions, have been observed. These impairments were found in various domains, such as attention, memory, executive functions, language, motor and visuomotor functions, among others. In line with contemporary research, other neurocognitive domains have recently been explored in TS, bringing evidence of altered social reasoning, for instance. Therefore, the aims of this review are to give an overview of the neuropsychological dimensions of TS, to report how neuropsychological functions evolve from childhood to adulthood, and to explain how various confounding factors can affect TS patients' performance in neuropsychological tasks. Finally, an important contribution of this review is to show how recent research has confirmed or changed our beliefs about neuropsychological functioning in TS.
MicroRNAs in Basolateral Amygdala Associated with Stress and Fear Memories Regulate Rapid Eye Movement Sleep in Rats.
Brain sciences, 2021

Stress-related sleep disturbances are distressing clinical symptoms in posttraumatic stress disorder patients. Intensely stressful events and their memories change rapid eye movement (REM) sleep in animal models. REM sleep varies with individual differences of stress resilience or vulnerability. The basolateral amygdala (BLA) is a primary mediator of the effects of stress and fear memories on sleep. However, the molecular mechanisms in BLA regulating the effects of fear conditioning, shock training (ST) and context re-exposure (CTX) on REM sleep are not well known. MicroRNAs (miRNAs) are small, non-coding RNAs and posttranscriptional gene regulators of diverse biological processes. The aim of this study is to investigate ST- and CTX-altered miRNAs in the BLA of resilience and vulnerable animals and on REM sleep regulation. MiRNAs expression profiles in BLA were generated following ST and CTX using the Taqman Low Density rodent microRNA array. The altered BLA miRNAs expression and REM sleep reduction observed in ST and CTX vulnerable animals. AntagomiR-221 microinjection into BLA for one of the upregulated miRNAs, miR-221 in BLA, attenuated the REM sleep reduction. This study suggests that miRNAs in the BLA may play a significant role in mediating the effects of stress and fear memories on REM sleep.
The role of noradrenaline and 5-hydroxytryptamine in yohimbine-induced increases in alcohol-seeking in rats.
Psychopharmacology, 2009

We previously showed that systemic administration of the prototypical alpha-2 noradrenaline (NA) receptor antagonist yohimbine increases alcohol self-administration and reinstatement. Yohimbine also acts as an agonist of 5-hydroxytryptamine (5-HT) 5-HT1A receptors, which have been shown to be involved in alcohol seeking. Here, we determined the contributions of the alpha-2 and 5-HT1A properties of yohimbine to its effects on alcohol seeking.
Mirtazapine has a therapeutic potency in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mice model of Parkinson's disease.
BMC neuroscience, 2014

Mirtazapine, a noradrenergic and specific serotonergic antidepressant (NaSSA), shows multiple pharmacological actions such as inhibiting presynaptic α2 noradrenaline receptor (NAR) and selectively activating 5-hydroxytriptamine (5-HT) 1A receptor (5-HT1AR). Mirtazapine was also reported to increase dopamine release in the cortical neurons with 5-HT dependent manner. To examine whether mirtazapine has a therapeutic potency in Parkinson's disease (PD), we examined this compound in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice model of PD.
French clinical guidelines for peripheral motor nerve blocks in a PRM setting.
Annals of physical and rehabilitation medicine, 2019

Motor nerve blocks with anesthetic drug for local anesthesia are commonly used in physical and rehabilitation medicine (PRM), especially in the field of spasticity. Guidelines in this context are currently lacking.
Hypersensitive assessment of aryl hydrocarbon receptor transcriptional activity using a novel truncated cyp1a promoter in zebrafish.
FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2018

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a persistent organic pollutant (POP), an unintentional byproduct of various industrial processes, and a human carcinogen. The expression of the cytochrome P450 1A (cyp1a) gene is upregulated in the presence of TCDD through activating the aryl hydrocarbon receptor pathway in a dose-dependent manner. Several essential response elements, including the 8 potential xenobiotic response elements in the cyp1a promoter region, have been identified to be the main functional parts for the response to TCDD. Thus, we aimed to develop a convenient and sensitive biomonitoring tool to examine the level of POPs in the environment and evaluate its potential human health risks by TCDD. Here, we established a transgenic zebrafish model with a red fluorescent reporter gene ( mCherry) using the truncated cyp1a promoter. Under exposure to TCDD, the expression pattern of mCherry in the reporter zebrafish mirrored that of endogenous cyp1a mRNA, and the primary target tissues for TCDD were the brain vessels, liver, gut, cloaca, and skin. Our results indicated that exposure of the embryos to TCDD at concentrations as low as 0.005 nM for 48 h, which did not elicit morphologic abnormalities in the embryos, markedly increased mCherry expression. In addition, the reporter embryos responded to other POPs, and primary liver cell culture of zebrafish revealed that Cyp1a protein was mainly expressed in the cytoplasm of liver cells. Furthermore, our transgenic fish embryos demonstrated that TCDD exposure can regulate the expression levels of several tumor-related factors, including epidermal growth factor, TNF-α, C-myc, proliferating cell nuclear antigen, TGF-β, serine/threonine kinase (Akt), and phosphorylated Akt, suggesting that our transgenic fish can be used as a sensitive model to evaluate the carcinogenicity induced by TCDD exposure.-Luo, J.-J., Su, D.-S., Xie, S.-L., Liu, Y., Liu, P., Yang, X.-J., Pei D.-S. Hypersensitive assessment of aryl hydrocarbon receptor transcriptional activity using a novel truncated cyp1a promoter in zebrafish.
An adeno-associated viral vector transduces the rat hypothalamus and amygdala more efficient than a lentiviral vector.
BMC neuroscience, 2010

This study compared the transduction efficiencies of an adeno-associated viral (AAV) vector, which was pseudotyped with an AAV1 capsid and encoded the green fluorescent protein (GFP), with a lentiviral (LV) vector, which was pseudotyped with a VSV-G envelop and encoded the discosoma red fluorescent protein (dsRed), to investigate which viral vector transduced the lateral hypothalamus or the amygdala more efficiently. The LV-dsRed and AAV1-GFP vector were mixed and injected into the lateral hypothalamus or into the amygdala of adult rats. The titers that were injected were 1 x 108 or 1 x 109 genomic copies of AAV1-GFP and 1 x 105 transducing units of LV-dsRed.
Improving Dignity of Care in Community-Dwelling Elderly Patients with Cognitive Decline and Their Caregivers. The Role of Dignity Therapy.
Behavioral sciences (Basel, Switzerland), 2020

Demographic changes have placed age-related mental health disorders at the forefront of public health challenges over the next three decades worldwide. Within the context of cognitive impairment and neurocognitive disorders among elderly people, the fragmentation of the self is associated with existential suffering, loss of meaning and dignity for the patient, as well as with a significant burden for the caregiver. Psychosocial interventions are part of a person-centered approach to cognitive impairment (including early stage dementia and dementia). Dignity therapy (DT) is a therapeutic intervention that has been shown to be effective in reducing existential distress, mood, and anxiety symptoms and improving dignity in persons with cancer and other terminal conditions in palliative care settings. The aims of this paper were: (i) To briefly summarize key issues and challenges related to care in gerontology considering specifically frail elderly/elderly with cognitive decline and their caregivers; and (ii) to provide a narrative review of the recent knowledge and evidence on DT in the elderly population with cognitive impairment. We searched the electronic data base (CINAHL, SCOPUS, PSycInfo, and PubMed studies) for studies regarding the application of DT in the elderly. Additionally, given the caregiver's role as a custodian of diachronic unity of the cared-for and the need to help caregivers to cope with their own existential distress and anticipatory grief, we also propose a DT-dyadic approach addressing the needs of the family as a whole.
Small angle X-ray scattering analysis of Cu(2+)-induced oligomers of the Alzheimer's amyloid β peptide.
Metallomics : integrated biometal science, 2015

Research into causes of Alzheimer's disease and its treatment has produced a tantalising array of hypotheses about the role of transition metal dyshomeostasis, many of them on the interaction of these metals with the neurotoxic amyloid-β peptide (Aβ). Here, we have used small angle X-ray scattering (SAXS) to study the effect of the molar ratio, Cu(2+)/Aβ, on the early three-dimensional structures of the Aβ1-40 and Cu(2+)/Aβ1-42 peptides in solution. We found that at molar ratios of 0.5 copper to peptide Aβ1-40 aggregated, while Aβ1-42 adopted a relatively monodisperse cylindrical shape, and at a ratio of 1.5 copper to peptide Aβ1-40 adopted a monodisperse cylindrical shape, while Aβ1-42 adopted the shape of an ellipsoid of rotation. We also found, via in-line rapid mixing SAXS analysis, that both peptides in the absence of copper were monodisperse at very short timeframes (<2 s). Kratky plots of these scattering profiles indicated that immediately after mixing both were intrinsically disordered. Ensemble optimisation modelling reflected this, indicating a wide range of structural conformers. These data reflect the ensembles from which the Cu(2+)-promoted oligomers were derived. Our results are discussed in the light of other studies that have shown that the Cu(2+)/Aβ has a marked effect on fibril and oligomer formation by this peptide, with a higher ratio favouring the formation of cytotoxic non-amyloid oligomers. Our results are relatively consistent with previous two-dimensional studies of the conformations of these Cu(2+)-induced entities, made on a much longer time-scale than SAXS, by transmission electron microscopy and atomic force microscopy, which showed that a range of oligomeric species are formed. We propose that SAXS carried out on a modern synchrotron beamline enables studies on initial events in disordered protein folding on physiologically-relevant time-scales, and will likely provide great insight into the initiating processes of the Aβ misfolding, oligomerisation and amyloid formation.
Transgenic fatal familial insomnia mice indicate prion infectivity-independent mechanisms of pathogenesis and phenotypic expression of disease.
PLoS pathogens, 2015

Fatal familial insomnia (FFI) and a genetic form of Creutzfeldt-Jakob disease (CJD178) are clinically different prion disorders linked to the D178N prion protein (PrP) mutation. The disease phenotype is determined by the 129 M/V polymorphism on the mutant allele, which is thought to influence D178N PrP misfolding, leading to the formation of distinctive prion strains with specific neurotoxic properties. However, the mechanism by which misfolded variants of mutant PrP cause different diseases is not known. We generated transgenic (Tg) mice expressing the mouse PrP homolog of the FFI mutation. These mice synthesize a misfolded form of mutant PrP in their brains and develop a neurological illness with severe sleep disruption, highly reminiscent of FFI and different from that of analogously generated Tg(CJD) mice modeling CJD178. No prion infectivity was detectable in Tg(FFI) and Tg(CJD) brains by bioassay or protein misfolding cyclic amplification, indicating that mutant PrP has disease-encoding properties that do not depend on its ability to propagate its misfolded conformation. Tg(FFI) and Tg(CJD) neurons have different patterns of intracellular PrP accumulation associated with distinct morphological abnormalities of the endoplasmic reticulum and Golgi, suggesting that mutation-specific alterations of secretory transport may contribute to the disease phenotype.
Evaluation of the pro-cognitive effects of the AMPA receptor positive modulator, 5-(1-piperidinylcarbonyl)-2,1,3-benzoxadiazole (CX691), in the rat.
Psychopharmacology, 2009

Positive allosteric modulators of the glutamatergic alpha-amino-3-hydroxy-5-methyl-4-isoazolepropionic acid (AMPA) receptor do not stimulate AMPA receptors directly but delay deactivation of the receptor and/or slow its desensitisation. This results in increased synaptic responses and enhanced long-term potentiation. Thus, it has been suggested that such compounds may have utility for the treatment of cognitive impairment.