rudyvdbrink/CitationDatabase huggingface dataset:
Involvement of Endogenous Enkephalins and β-Endorphin in Feeding and Diet-Induced Obesity.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2015

Studies implicate opioid transmission in hedonic and metabolic control of feeding, although roles for specific endogenous opioid peptides have barely been addressed. Here, we studied palatable liquid consumption in proenkephalin knockout (PENK KO) and β-endorphin-deficient (BEND KO) mice, and how the body weight of these mice changed during consumption of an energy-dense highly palatable 'cafeteria diet'. When given access to sucrose solution, PENK KOs exhibited fewer bouts of licking than wild types, even though the length of bouts was similar to that of wild types, a pattern that suggests diminished food motivation. Conversely, BEND KOs did not differ from wild types in the number of licking bouts, even though these bouts were shorter in length, suggesting that they experienced the sucrose as being less palatable. In addition, licking responses in BEND, but not PENK, KO mice were insensitive to shifts in sucrose concentration or hunger. PENK, but not BEND, KOs exhibited lower baseline body weights compared with wild types on chow diet and attenuated weight gain when fed cafeteria diet. Based on this and related findings, we suggest endogenous enkephalins primarily set a background motivational tone regulating feeding behavior, whereas β-endorphin underlies orosensory reward in high need states or when the stimulus is especially valuable. Overall, these studies emphasize complex interplays between endogenous opioid peptides targeting μ-receptors, such as enkephalins and endorphins, underlying the regulation of feeding and body weight that might explain the poor efficacy of drugs that generally target μ-opioid receptors in the long-term control of appetite and body weight.
Evolution of Locomotor Rhythms.
Trends in neurosciences, 2018

Nervous systems control locomotion using rhythmically active networks that orchestrate motor neuron firing patterns. Whether animals use common or distinct genetic programs to encode motor rhythmicity remains unclear. Cross-species comparisons have revealed remarkably conserved neural patterning systems but have also unveiled divergent circuit architectures that can generate similar locomotor behaviors.
Metabolism in Acute-On-Chronic Liver Failure: The Solution More than the Problem.
Archives of medical research, 2019

Chronic inflammatory liver disease with an acute deterioration of liver function is named acute-on-chronic inflammation and could be regulated by the metabolic impairments related to the liver dysfunction. In this way, the experimental cholestasis model is excellent for studying metabolism in both types of inflammatory responses. Along the evolution of this model, the rats develop biliary fibrosis and an acute-on-chronic decompensation. The acute decompensation of the liver disease is associated with encephalopathy, ascites, acute renal failure, an acute phase response and a splanchnic increase of pro- and anti-inflammatory cytokines. This multiorgan inflammatory dysfunction is mainly associated with a splanchnic and systemic metabolic switch with dedifferentiation of the epithelial, endothelial and mesothelial splanchnic barriers. Furthermore, a splanchnic infiltration by mast cells occurs, which suggests that these cells could carry out a compensatory metabolic role, especially through the modulation of hepatic and extrahepatic mitochondrial-peroxisome crosstalk. For this reason, we propose the hypothesis that mastocytosis in the acute-on-chronic hepatic insufficiency could represent the development of a survival metabolic mechanisms that mitigates the noxious effect of the hepatic functional deficit. A better understanding the pathophysiological response of the mast cells in liver insufficiency and portal hypertension would help to find new pathways for decreasing the high morbidity and mortality rate of these patients.
Cerebral Autoregulation in Stroke.
Current atherosclerosis reports, 2018

Cerebral autoregulation (CA) is a mechanism that maintains cerebral blood flow constant despite fluctuations in systemic arterial blood pressure. This review will focus on recent studies that measured CA non-invasively in acute cerebrovascular events, a feature unique to the transcranial Doppler ultrasound. We will summarize the rationale for CA assessment in acute cerebrovascular disorders and specifically evaluate the existing data on the value of CA measures in relation to clinical severity, guiding management decisions, and prognostication.
Topoisomerase inhibitors: Pharmacology and emerging nanoscale delivery systems.
Pharmacological research, 2020

Topoisomerase enzymes have shown unique roles in replication and transcription. These enzymes which were initially found in Escherichia coli have attracted considerable attention as target molecules for cancer therapy. Nowadays, there are several topoisomerase inhibitors in the market to treat or at least control the progression of cancer. However, significant toxicity, low solubility and poor pharmacokinetic properties have limited their wide application and these characteristics need to be improved. Nano-delivery systems have provided an opportunity to modify the intrinsic properties of molecules and also to transfer the toxic agent to the target tissues. These delivery systems leads to the re-introduction of existing molecules present in the market as novel therapeutic agents with different physicochemical and pharmacokinetic properties. This review focusses on a variety of nano-delivery vehicles used for the improvement of pharmacological properties of topoisomerase inhibitors and thus enabling their potential application as novel drugs in the market.
Comparisons of responses by planarian to micromolar to attomolar dosages of morphine or naloxone and/or weak pulsed magnetic fields: revealing receptor subtype affinities and non-specific effects.
International journal of radiation biology, 2014

The behavioral responses of planaria to the exposures of a range of concentrations of morphine (μM to attoM) or the μ-opiate antagonist naloxone or to either of these compounds and a burst-firing magnetic field (5 μT) were studied.
Executive functions in intellectual disabilities: a comparison between Williams syndrome and Down syndrome.
Research in developmental disabilities, 2013

Executive functions are a set of high cognitive abilities that control and regulate other functions and behaviors and are crucial for successful adaptation. Deficits in executive functions are frequently described in developmental disorders, which are characterized by disadaptive behavior. However, executive functions are not widely examined in individuals with intellectual disability. The present study is aimed at evaluating the etiological specificity hypotheses pertaining to executive functions by comparing individuals with intellectual disability of different etiology, as Williams syndrome and Down syndrome, on different aspects of executive functions. To this aim a battery evaluating attention, short-term and working memory, planning, categorization, shifting and inhibition, was administered to 15 children, adolescents and adults with Williams syndrome, to 15 children, adolescents and adults with Down syndrome and to 16 mental-age-matched typically developing children. The two groups with intellectual disability showed impairment in a set of executive functions, as auditory sustained attention, visual selective attention, visual categorization and working memory, and preserved visual sustained attention, auditory selective attention and visual inhibition. However, a distinctive profile has been found between the two syndromic groups on other executive functions. While participants with Down syndrome were poor in shifting and verbal aspects of memory and inhibition, those with Williams syndrome were poor in planning. The specific weakness and straights on executive functions may support the etiological specificity hypothesis accounting for distinctive cognitive development syndrome-specific.
The role of machine learning in neuroimaging for drug discovery and development.
Psychopharmacology, 2015

Neuroimaging has been identified as a potentially powerful probe for the in vivo study of drug effects on the brain with utility across several phases of drug development spanning preclinical and clinical investigations. Specifically, neuroimaging can provide insight into drug penetration and distribution, target engagement, pharmacodynamics, mechanistic action and potential indicators of clinical efficacy. In this review, we focus on machine learning approaches for neuroimaging which enable us to make predictions at the individual level based on the distributed effects across the whole brain. Crucially, these approaches can be trained on data from one study and applied to an independent study and, unlike group-level statistics, can be readily use to assess the generalisability to unseen data. In this review, we present examples and suggestions for how machine learning could help answer fundamental questions spanning the drug discovery pipeline: (1) Who should I recruit for this study? (2) What should I measure and when should I measure it? (3) How does the pharmacological agent behave using an experimental medicine model?, and (4) How does a compound differ from and/or resemble existing compounds? Specifically, we present studies from the literature and we suggest areas for the focus of future development. Further refinement and tailoring of machine learning techniques may help realise their tremendous potential for drug discovery and drug validation.
Mental health services during the first wave of the COVID-19 pandemic in Europe: Results from the EPA Ambassadors Survey and implications for clinical practice.
European psychiatry : the journal of the Association of European Psychiatrists, 2021

The COVID-19 pandemic caused an unprecedented worldwide crisis affecting several sectors, including health, social care, economy and society at large. The World Health Organisation has emphasized that mental health care should be considered as one of the core sectors within the overall COVID-19 health response. By March 2020, recommendations for the organization of mental health services across Europe have been developed by several national and international mental health professional associations.
Air pollution impairs cognition, provokes depressive-like behaviors and alters hippocampal cytokine expression and morphology.
Molecular psychiatry, 2011

Particulate matter air pollution is a pervasive global risk factor implicated in the genesis of pulmonary and cardiovascular disease. Although the effects of prolonged exposure to air pollution are well characterized with respect to pulmonary and cardiovascular function, comparatively little is known about the impact of particulate matter on affective and cognitive processes. The central nervous system may be adversely affected by activation of reactive oxygen species and pro-inflammatory pathways that accompany particulate matter pollution. Thus, we investigated whether long-term exposure to ambient fine airborne particulate matter (<2.5 μm (PM(2.5))) affects cognition, affective responses, hippocampal inflammatory cytokines and neuronal morphology. Male mice were exposed to either PM(2.5) or filtered air (FA) for 10 months. PM(2.5) mice displayed more depressive-like responses and impairments in spatial learning and memory as compared with mice exposed to FA. Hippocampal pro-inflammatory cytokine expression was elevated among PM(2.5) mice. Apical dendritic spine density and dendritic branching were decreased in the hippocampal CA1 and CA3 regions, respectively, of PM(2.5) mice. Taken together, these data suggest that long-term exposure to particulate air pollution levels typical of exposure in major cities around the globe can alter affective responses and impair cognition.
Modelling associations between neurocognition and functional course in young people with emerging mental disorders: a longitudinal cohort study.
Translational psychiatry, 2020

Neurocognitive impairment is commonly associated with functional disability in established depressive, bipolar and psychotic disorders. However, little is known about the longer-term functional implications of these impairments in early phase transdiagnostic cohorts. We aimed to examine associations between neurocognition and functioning at baseline and over time. We used mixed effects models to investigate associations between neurocognitive test scores and longitudinal social and occupational functioning ("Social and Occupational Functioning Assessment Scale") at 1-7 timepoints over five-years in 767 individuals accessing youth mental health services. Analyses were adjusted for age, sex, premorbid IQ, and symptom severity. Lower baseline functioning was associated with male sex (coefficient -3.78, 95% CI -5.22 to -2.34 p < 0.001), poorer verbal memory (coefficient 0.90, 95% CI 0.42 to 1.38, p < 0.001), more severe depressive (coefficient -0.28, 95% CI -0.41 to -0.15, p < 0.001), negative (coefficient -0.49, 95% CI -0.74 to -0.25, p < 0.001), and positive symptoms (coefficient -0.25, 95% CI -0.41 to -0.09, p = 0.002) and lower premorbid IQ (coefficient 0.13, 95% CI 0.07 to 0.19, p < 0.001). The rate of change in functioning over time varied among patients depending on their sex (male; coefficient 0.73, 95% CI 0.49 to 0.98, p < 0.001) and baseline level of cognitive flexibility (coefficient 0.14, 95% CI 0.06 to 0.22, p < 0.001), such that patients with the lowest scores had the least improvement in functioning. Impaired cognitive flexibility is common and may represent a meaningful and transdiagnostic target for cognitive remediation in youth mental health settings. Future studies should pilot cognitive remediation targeting cognitive flexibility while monitoring changes in functioning.
PET Imaging in Glioma: The Neuro-Oncologist's Expectations.
PET clinics, 2013

PET-imaging is a useful tool for management of certain glioma patients. The variable availability of adequate tracers, their short half-life, but also administrative obstacles and financial constraints are hampering the prospective evaluation of PET. Its impact in tumor localization and accurate diagnosis, in treatment response evaluation and ultimately patient outcome needs to be demonstrated. Systematic algorithms for optimal and economical use are needed. We summarize the limitations of the usual imaging techniques, and of the added value of PET-imaging in specific clinical situations. We call for prospective studies and registries rather than the current largely resource-driven use of this valuable technique.
Keratitis in Dry Eye Disease and Topical Ciclosporin A.
Ocular immunology and inflammation, 2017

Tear film alterations in dry eye disease (DED) include reduced tear volume and an increase in inflammatory cytokines. Instability and reduced tear production initiate a vicious cycle where hyperosmolarity, ocular inflammation, and apoptosis may induce damage of the ocular surface including keratitis. Topical cyclosporine (CsA) has been used for the treatment of moderate-to-severe DED; however, previous studies failed to demonstrate its benefits by the European Agency standards. A new formulation of CsA 0.1% has been recently approved in the EU to treat severe keratitis in DED patients. Patients with severe keratitis showed a better improvement after 6 months of treatment with CsA compared with vehicle. HLA-DR expression was significantly reduced by CsA treatment. The clinically significant improvement in keratitis associated with the inflammatory biomarker HLA-DR confirms the efficacy of CsA to improve inflammation and its damaging effect on the ocular surface in DED patients.
Protein expression of targets of the FMRP regulon is altered in brains of subjects with schizophrenia and mood disorders.
Schizophrenia research, 2015

Fragile X mental retardation protein (FMRP) is an RNA binding protein with 842 target mRNAs in mammalian brain. Silencing of the fragile X mental retardation 1 (FMR1) gene leads to loss of expression of FMRP and upregulated metabotropic glutamate receptor 5 (mGluR5) signaling resulting in the multiple physical and cognitive deficits associated with fragile X syndrome (FXS). Reduced FMRP expression has been identified in subjects with autism, schizophrenia, bipolar disorder, and major depression who do not carry the mutation for FMR1. Our laboratory has recently demonstrated altered expression of four downstream targets of FMRP-mGluR5 signaling in brains of subjects with autism: homer 1, amyloid beta A4 precursor protein (APP), ras-related C3 botulinum toxin substrate 1 (RAC1), and striatal-enriched protein tyrosine phosphatase (STEP). In the current study we investigated the expression of the same four proteins in lateral cerebella of subjects with schizophrenia, bipolar disorder, and major depression and in frontal cortex of subjects with schizophrenia and bipolar disorder. In frontal cortex we observed: 1) reduced expression of 120 kDa form of APP in subjects with schizophrenia and bipolar disorder; 2) reduced expression of 61 kDa and 33k Da forms of STEP in subjects with schizophrenia; 3) reduced expression of 88 kDa form of APP in subjects with bipolar disorder; and 3) trends for reduced expression of 88 kDa form of APP and homer 1 in subjects with schizophrenia and bipolar disorder, respectively. In lateral cerebella there was no group difference, however we observed increased expression of RAC1 in subjects with bipolar disorder, and trends for increased RAC1 in subjects with schizophrenia and major depression. Our results provide further evidence that proteins involved in the FMRP-mGluR5 signaling pathway are altered in schizophrenia and mood disorders.
Post-tetanic increase in the fast-releasing synaptic vesicle pool at the expense of the slowly releasing pool.
The Journal of general physiology, 2010

Post-tetanic potentiation (PTP) at the calyx of Held synapse is caused by increases not only in release probability (P(r)) but also in the readily releasable pool size estimated from a cumulative plot of excitatory post-synaptic current amplitudes (RRP(cum)), which contribute to the augmentation phase and the late phase of PTP, respectively. The vesicle pool dynamics underlying the latter has not been investigated, because PTP is abolished by presynaptic whole-cell patch clamp. We found that supplement of recombinant calmodulin to the presynaptic pipette solution rescued the increase in the RRP(cum) after high-frequency stimulation (100 Hz for 4-s duration, HFS), but not the increase in P(r). Release-competent synaptic vesicles (SVs) are heterogeneous in their releasing kinetics. To investigate post-tetanic changes of fast and slowly releasing SV pool (FRP and SRP) sizes, we estimated quantal release rates before and 40 s after HFS using the deconvolution method. After HFS, the FRP size increased by 19.1% and the SRP size decreased by 25.4%, whereas the sum of FRP and SRP sizes did not increase. Similar changes in the RRP were induced by a single long depolarizing pulse (100 ms). The post-tetanic complementary changes of FRP and SRP sizes were abolished by inhibitors of myosin II or myosin light chain kinase. The post-tetanic increase in the FRP size coupled to a decrease in the SRP size provides the first line of evidence for the idea that a slowly releasing SV can be converted to a fast releasing one.
Genome-wide association study of NMDA receptor coagonists in human cerebrospinal fluid and plasma.
Molecular psychiatry, 2015

The N-methyl-D-aspartate receptor (NMDAR) coagonists glycine, D-serine and L-proline play crucial roles in NMDAR-dependent neurotransmission and are associated with a range of neuropsychiatric disorders. We conducted the first genome-wide association study of concentrations of these coagonists and their enantiomers in plasma and cerebrospinal fluid (CSF) of human subjects from the general population (N=414). Genetic variants at chromosome 22q11.2, located in and near PRODH (proline dehydrogenase), were associated with L-proline in plasma (β=0.29; P=6.38 × 10(-10)). The missense variant rs17279437 in the proline transporter SLC6A20 was associated with L-proline in CSF (β=0.28; P=9.68 × 10(-9)). Suggestive evidence of association was found for the D-serine plasma-CSF ratio at the D-amino-acid oxidase (DAO) gene (β=-0.28; P=9.08 × 10(-8)), whereas a variant in SRR (that encodes serine racemase and is associated with schizophrenia) constituted the most strongly associated locus for the L-serine to D-serine ratio in CSF. All these genes are highly expressed in rodent meninges and choroid plexus, anatomical regions relevant to CSF physiology. The enzymes and transporters they encode may be targeted to further construe the nature of NMDAR coagonist involvement in NMDAR gating. Furthermore, the highlighted genetic variants may be followed up in clinical populations, for example, schizophrenia and 22q11 deletion syndrome. Overall, this targeted metabolomics approach furthers the understanding of NMDAR coagonist concentration variability and sets the stage for non-targeted CSF metabolomics projects.
Behavioral and other phenotypes in a cytoplasmic Dynein light intermediate chain 1 mutant mouse.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011

The cytoplasmic dynein complex is fundamentally important to all eukaryotic cells for transporting a variety of essential cargoes along microtubules within the cell. This complex also plays more specialized roles in neurons. The complex consists of 11 types of protein that interact with each other and with external adaptors, regulators and cargoes. Despite the importance of the cytoplasmic dynein complex, we know comparatively little of the roles of each component protein, and in mammals few mutants exist that allow us to explore the effects of defects in dynein-controlled processes in the context of the whole organism. Here we have taken a genotype-driven approach in mouse (Mus musculus) to analyze the role of one subunit, the dynein light intermediate chain 1 (Dync1li1). We find that, surprisingly, an N235Y point mutation in this protein results in altered neuronal development, as shown from in vivo studies in the developing cortex, and analyses of electrophysiological function. Moreover, mutant mice display increased anxiety, thus linking dynein functions to a behavioral phenotype in mammals for the first time. These results demonstrate the important role that dynein-controlled processes play in the correct development and function of the mammalian nervous system.