rudyvdbrink/CitationDatabase huggingface dataset:
A role for adenosine A(1) receptor blockade in the ability of caffeine to promote MDMA "Ecstasy"-induced striatal dopamine release.
European journal of pharmacology, 2011

Co-administration of caffeine profoundly enhances the acute toxicity of 3,4 methylenedioxymethamphetamine (MDMA) in rats. The aim of this study was to determine the ability of caffeine to impact upon MDMA-induced dopamine release in superfused brain tissue slices as a contributing factor to this drug interaction. MDMA (100 and 300μM) induced a dose-dependent increase in dopamine release in striatal and hypothalamic tissue slices preloaded with [(3)H] dopamine (1μM). Caffeine (100μM) also induced dopamine release in the striatum and hypothalamus, albeit to a much lesser extent than MDMA. When striatal tissue slices were superfused with MDMA (30μM) in combination with caffeine (30μM), caffeine enhanced MDMA-induced dopamine release, provoking a greater response than that obtained following either caffeine or MDMA applications alone. The synergistic effects in the striatum were not observed in hypothalamic slices. As adenosine A(1) receptors are, one of the main pharmacological targets of caffeine, which are known to play an important role in the regulation of dopamine release, their role in the modulation of MDMA-induced dopamine release was investigated. 1μM 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), a specific A(1) antagonist, like caffeine, enhanced MDMA-induced dopamine release from striatal slices while 1μM 2,chloro-N(6)-cyclopentyladenosine (CCPA), a selective adenosine A(1) receptor agonist, attenuated this. Treatment with either SCH 58261, a selective A(2A) receptor antagonist, or rolipram, a selective PDE-4 inhibitor, failed to reproduce a caffeine-like effect on MDMA-induced dopamine release. These results suggest that caffeine regulates MDMA-induced dopamine release in striatal tissue slices, via inhibition of adenosine A(1) receptors.
Muscle Satellite Cell Cross-Talk with a Vascular Niche Maintains Quiescence via VEGF and Notch Signaling.
Cell stem cell, 2018

Skeletal muscle is a complex tissue containing tissue resident muscle stem cells (satellite cells) (MuSCs) important for postnatal muscle growth and regeneration. Quantitative analysis of the biological function of MuSCs and the molecular pathways responsible for a potential juxtavascular niche for MuSCs is currently lacking. We utilized fluorescent reporter mice and muscle tissue clearing to investigate the proximity of MuSCs to capillaries in 3 dimensions. We show that MuSCs express abundant VEGFA, which recruits endothelial cells (ECs) in vitro, whereas blocking VEGFA using both a vascular endothelial growth factor (VEGF) inhibitor and MuSC-specific VEGFA gene deletion reduces the proximity of MuSCs to capillaries. Importantly, this proximity to the blood vessels was associated with MuSC self-renewal in which the EC-derived Notch ligand Dll4 induces quiescence in MuSCs. We hypothesize that MuSCs recruit capillary ECs via VEGFA, and in return, ECs maintain MuSC quiescence though Dll4.
Axon regeneration can facilitate or suppress hindlimb function after olfactory ensheathing glia transplantation.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011

Reports based primarily on anatomical evidence suggest that olfactory ensheathing glia (OEG) transplantation promotes axon regeneration across a complete spinal cord transection in adult rats. Based on functional, electrophysiological, and anatomical assessments, we found that OEG promoted axon regeneration across a complete spinal cord transection and that this regeneration altered motor responses over time. At 7 months after transection, 70% of OEG-treated rats showed motor-evoked potentials in hindlimb muscles after transcranial electric stimulation. Furthermore, a complete spinal cord retransection performed 8 months after injury demonstrated that this axon regeneration suppressed locomotor performance and decreased the hypersensitive hindlimb withdrawal response to mechanical stimulation. OEG transplantation alone promoted reorganization of lumbosacral locomotor networks and, when combined with long-term training, enhanced some stepping measures. These novel findings demonstrate that OEG promote regeneration of mature axons across a complete transection and reorganization of spinal circuitry, both of which contribute to sensorimotor function.
Author Correction: Inflammasome signalling in brain function and neurodegenerative disease.
Nature reviews. Neuroscience, 2019

In the originally published version of this article, the competing interests statement indicated that the authors had no competing interests; however, this statement was incorrect. The statement should have read as follows: 'M.H. receives a consultation fee from IFM Therapeutics, LLC for consultations regarding the pathogenesis and interventional strategies of neurodegenerative disease. E.L. is a scientific co-founder and consultant to IFM Therapeutics. R.M.M. declares no competing interests.' This error has been corrected in the HTML and PDF versions of the article.
CYP2C19 and 3A4 Dominate Metabolic Clearance and Bioactivation of Terbinafine Based on Computational and Experimental Approaches.
Chemical research in toxicology, 2019

Lamisil (terbinafine) is an effective, widely prescribed antifungal drug that causes rare idiosyncratic hepatotoxicity. The proposed toxic mechanism involves a reactive metabolite, 6,6-dimethyl-2-hepten-4-ynal (TBF-A), formed through three N-dealkylation pathways. We were the first to characterize them using in vitro studies with human liver microsomes and modeling approaches, yet knowledge of the individual enzymes catalyzing reactions remained unknown. Herein, we employed experimental and computational tools to assess terbinafine metabolism by specific cytochrome P450 isozymes. In vitro inhibitor phenotyping studies revealed six isozymes were involved in one or more N-dealkylation pathways. CYP2C19 and 3A4 contributed to all pathways, and so, we targeted them for steady-state analyses with recombinant isozymes. N-Dealkylation yielding TBF-A directly was catalyzed by CYP2C19 and 3A4 similarly. Nevertheless, CYP2C19 was more efficient than CYP3A4 at N-demethylation and other steps leading to TBF-A. Unlike microsomal reactions, N-denaphthylation was surprisingly efficient for CYP2C19 and 3A4, which was validated by controls. CYP2C19 was the most efficient among all reactions. Nonetheless, CYP3A4 was more selective at steps leading to TBF-A, making it more effective in terbinafine bioactivation based on metabolic split ratios for competing pathways. Model predictions did not extrapolate to quantitative kinetic constants, yet some results for CYP3A4 and CYP2C19 agreed qualitatively with preferred reaction steps and pathways. Clinical data on drug interactions support the CYP3A4 role in terbinafine metabolism, while CYP2C19 remains understudied. Taken together, knowledge of P450s responsible for terbinafine metabolism and TBF-A formation provides a foundation for investigating and mitigating the impact of P450 variations in toxic risks posed to patients.
Autologous hematopoietic stem cell transplantation in neuromyelitis optica: a registry study of the EBMT Autoimmune Diseases Working Party.
Multiple sclerosis (Houndmills, Basingstoke, England), 2015

Neuromyelitis optica (NMO) is an inflammatory autoimmune disorder of the central nervous system, hallmarked by pathogenic anti-aquaporin 4 antibodies. NMO prognosis is worse compared with multiple sclerosis.
Temporal-spatial characteristics of phase-amplitude coupling in electrocorticogram for human temporal lobe epilepsy.
Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology, 2017

Neural activity of the epileptic human brain contains low- and high-frequency oscillations in different frequency bands, some of which have been used as reliable biomarkers of the epileptogenic brain areas. However, the relationship between the low- and high-frequency oscillations in different cortical areas during the period from pre-seizure to post-seizure has not been completely clarified.
FIND--a unified framework for neural data analysis.
Neural networks : the official journal of the International Neural Network Society, 2008

The complexity of neurophysiology data has increased tremendously over the last years, especially due to the widespread availability of multi-channel recording techniques. With adequate computing power the current limit for computational neuroscience is the effort and time it takes for scientists to translate their ideas into working code. Advanced analysis methods are complex and often lack reproducibility on the basis of published descriptions. To overcome this limitation we develop FIND (Finding Information in Neural Data) as a platform-independent, open source framework for the analysis of neuronal activity data based on Matlab (Mathworks). Here, we outline the structure of the FIND framework and describe its functionality, our measures of quality control, and the policies for developers and users. Within FIND we have developed a unified data import from various proprietary formats, simplifying standardized interfacing with tools for analysis and simulation. The toolbox FIND covers a steadily increasing number of tools. These analysis tools address various types of neural activity data, including discrete series of spike events, continuous time series and imaging data. Additionally, the toolbox provides solutions for the simulation of parallel stochastic point processes to model multi-channel spiking activity. We illustrate two examples of complex analyses with FIND tools: First, we present a time-resolved characterization of the spiking irregularity in an in vivo extracellular recording from a mushroom-body extrinsic neuron in the honeybee during odor stimulation. Second, we describe layer specific input dynamics in the rat primary visual cortex in vivo in response to visual flash stimulation on the basis of multi-channel spiking activity.
Early-adolescent antibiotic exposure results in mitochondrial and behavioral deficits in adult male mice.
Scientific reports, 2021

Exposure to antibiotic treatment has been associated with increased vulnerability to various psychiatric disorders. However, a research gap exists in understanding how adolescent antibiotic therapy affects behavior and cognition. Many antibiotics that target bacterial translation may also affect mitochondrial translation resulting in impaired mitochondrial function. The brain is one of the most metabolically active organs, and hence is the most vulnerable to impaired mitochondrial function. We hypothesized that exposure to antibiotics during early adolescence would directly affect brain mitochondrial function, and result in altered behavior and cognition. We administered amoxicillin, chloramphenicol, or gentamicin in the drinking water to young adolescent male wild-type mice. Next, we assayed mitochondrial oxidative phosphorylation complex activities in the cerebral cortex, performed behavioral screening and targeted mass spectrometry-based acylcarnitine profiling in the cerebral cortex. We found that mice exposed to chloramphenicol showed increased repetitive and compulsive-like behavior in the marble burying test, an accurate and sensitive assay of anxiety, concomitant with decreased mitochondrial complex IV activity. Our results suggest that only adolescent chloramphenicol exposure leads to impaired brain mitochondrial complex IV function, and could therefore be a candidate driver event for increased anxiety-like and repetitive, compulsive-like behaviors.
Hypothalamic-pituitary-adrenal axis genetic variation and early stress moderates amygdala function.
Psychoneuroendocrinology, 2017

Early life stress may precipitate psychopathology, at least in part, by influencing amygdala function. Converging evidence across species suggests that links between childhood stress and amygdala function may be dependent upon hypothalamic-pituitary-adrenal (HPA) axis function. Using data from college-attending non-Hispanic European-Americans (n=308) who completed the Duke Neurogenetics Study, we examined whether early life stress (ELS) and HPA axis genetic variation interact to predict threat-related amygdala function as well as psychopathology symptoms. A biologically-informed multilocus profile score (BIMPS) captured HPA axis genetic variation (FKBP5 rs1360780, CRHR1 rs110402; NR3C2 rs5522/rs4635799) previously associated with its function (higher BIMPS are reflective of higher HPA axis activity). BOLD fMRI data were acquired while participants completed an emotional face matching task. ELS and depression and anxiety symptoms were measured using the childhood trauma questionnaire and the mood and anxiety symptom questionnaire, respectively. The interaction between HPA axis BIMPS and ELS was associated with right amygdala reactivity to threat-related stimuli, after accounting for multiple testing (empirical-p=0.016). Among individuals with higher BIMPS (i.e., the upper 21.4%), ELS was positively coupled with threat-related amygdala reactivity, which was absent among those with average or low BIMPS. Further, higher BIMPS were associated with greater self-reported anxious arousal, though there was no evidence that amygdala function mediated this relationship. Polygenic variation linked to HPA axis function may moderate the effects of early life stress on threat-related amygdala function and confer risk for anxiety symptomatology. However, what, if any, neural mechanisms may mediate the relationship between HPA axis BIMPS and anxiety symptomatology remains unclear.
Autophagy gone awry in neurodegenerative diseases.
Nature neuroscience, 2010

Autophagy is essential for neuronal homeostasis, and its dysfunction has been directly linked to a growing number of neurodegenerative disorders. The reasons behind autophagic failure in degenerating neurons can be very diverse because of the different steps required for autophagy and the characterization of the molecular players involved in each of them. Understanding the step(s) affected in the autophagic process in each disorder could explain differences in the course of these pathologies and will be essential to developing targeted therapeutic approaches for each disease based on modulation of autophagy. Here we present examples of different types of autophagic dysfunction described in common neurodegenerative disorders and discuss the prospect of exploring some of the recently identified autophagic variants and the interactions among autophagic and non-autophagic proteolytic systems as possible future therapeutic targets.
Use of vivo-morpholinos for control of protein expression in the adult rat brain.
Journal of neuroscience methods, 2012

Vivo-morpholinos are commercially available morpholino oligomers with a terminal octa-guanidinium dendrimer for enhanced cell-permeability. Existing evidence from systemically delivered vivo-morpholinos indicate that genetic suppression can last from days to weeks without evidence of cellular toxicity. However, intravenously delivered vivo-morpholinos are ineffective at protein suppression in the brain, and no evidence is available regarding whether intracranially delivered vivo-morpholinos effectively reduce target protein levels, or do so without inducing neurotoxicity. Here we report examples in which in vivo microinjection of antisense vivo-morpholinos directed against three different targets (xCT, GLT1, orexin) in two different brain regions resulted in significant suppression of protein expression without neurotoxicity. Expression was significantly suppressed at six to seven days post-administration, but returned to baseline levels within fourteen days. These results indicate that direct intracranial administration of vivo-morpholinos provides an effective means by which to suppress protein expression in the brain for one to two weeks.
Phosphodiesterase type 2 distribution in the guinea pig urinary bladder.
World journal of urology, 2015

Nitric oxide-stimulated cGMP synthesis represents an important signalling pathway in the urinary bladder. Inhibitors of the PDE1 and PDE5 enzyme have been studied to treat storage and voiding disorders in clinical settings. The distribution of PDE2 in the bladder is unknown. This study focuses on the distribution and site of action of PDE2 within the guinea pig urinary bladder wall.
Metabotropic glutamate receptors in median preoptic neurons modulate neuronal excitability and glutamatergic and GABAergic inputs from the subfornical organ.
Journal of neurophysiology, 2010

Cardiovascular and behavioral responses to circulating angiotensin require intact connectivity along the upper lamina terminalis joining the subfornical organ (SFO) with the median preoptic nucleus (MnPO). In the present study on MnPO neurons, we used whole cell patch-clamp recording techniques in brain slice preparations to evaluate the influence of metabotropic glutamate receptor (mGluR) agonists on modulating their intrinsic excitability and SFO-evoked glutamatergic and GABAergic postsynaptic currents. In 22/36 cells, bath application of a mGluR group I agonist (S)-3,5-dihydroxyphenylglycine (DHPG) induced a TTX-resistant inward current coupled with decrease in a membrane K(+) conductance but also a possible increase in a nonselective cationic conductance. By contrast, 27/49 cells responded to a mGluR group II agonist (2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DCG IV) with a TTX-resistant outward current and increase in membrane conductance that reversed around -95 mV, suggesting opening of K(+) channels. None of 19 cells responded to the mGluR group III agonist l-(+)-2-amino-4-phosphonobutyric acid (l-AP4). Agonists for all mGluR groups suppressed SFO-evoked excitatory postsynaptic currents and significantly increased paired-pulse ratios, implying a presynaptic mechanism. Only the mGluR group II agonist significantly reduced SFO-evoked inhibitory postsynaptic currents and caused an increase in paired-pulse ratios. These results suggest a complexity of pre- and postsynaptic mGluRs are available to modulate rapid neurotransmission along the upper lamina terminalis from SFO to MnPO.
Transplantation of mesenchymal stem cells overexpressing interleukin-10 induces autophagy response and promotes neuroprotection in a rat model of TBI.
Journal of cellular and molecular medicine, 2019

Autophagy, including mitophagy, is critical for neuroprotection in traumatic brain injury (TBI). Transplantation of mesenchymal stem cells (MSCs) provides neuroprotection and induces autophagy by increasing anti-inflammatory cytokines, such as interleukin-10 (IL-10). To evaluate these effects of IL10 that are released by MSCs, we genetically engineered MSCs to overexpress IL10 and compared their effects to unaltered MSCs following transplantation near the site of induced TBIs in rats. Adult, male Sprague-Dawley rats were divided into four groups: Sham + vehicle, TBI + vehicle, TBI + MSCs-IL-10 and TBI + MSCs-GFP. Thirty-six hours post-TBI, the first two groups received vehicle (Hanks balance salt solution), whereas last two groups were transplanted with MSCs-IL-10 or MSCs-GFP. Three weeks after transplantation, biomarkers for neurodegenerative changes, autophagy, mitophagy, cell death and survival markers were measured. We observed a significant increase in the number of dead cells in the cortex and hippocampus in TBI rats, whereas transplantation of MSCs-IL-10 significantly reduced their numbers in comparison to MSCs alone. MSCs-IL-10 rats had increased autophagy, mitophagy and cell survival markers, along with decreased markers for cell death and neuroinflammation. These results suggest that transplantation of MSCs-IL-10 may be an effective strategy to protect against TBI-induced neuronal damage.
Human processing of behaviorally relevant and irrelevant absence of expected rewards: a high-resolution ERP study.
PloS one, 2011

Acute lesions of the posterior medial orbitofrontal cortex (OFC) in humans may induce a state of reality confusion marked by confabulation, disorientation, and currently inappropriate actions. This clinical state is strongly associated with an inability to abandon previously valid anticipations, that is, extinction capacity. In healthy subjects, the filtering of memories according to their relation with ongoing reality is associated with activity in posterior medial OFC (area 13) and electrophysiologically expressed at 220-300 ms. These observations indicate that the human OFC also functions as a generic reality monitoring system. For this function, it is presumably more important for the OFC to evaluate the current behavioral appropriateness of anticipations rather than their hedonic value. In the present study, we put this hypothesis to the test. Participants performed a reversal learning task with intermittent absence of reward delivery. High-density evoked potential analysis showed that the omission of expected reward induced a specific electrocortical response in trials signaling the necessity to abandon the hitherto reward predicting choice, but not when omission of reward had no such connotation. This processing difference occurred at 200-300 ms. Source estimation using inverse solution analysis indicated that it emanated from the posterior medial OFC. We suggest that the human brain uses this signal from the OFC to keep thought and behavior in phase with reality.
Analogous mechanism regulating formation of neocortical basal radial glia and cerebellar Bergmann glia.
eLife, 2017

Neocortical basal radial glia (bRG) and cerebellar Bergmann glia (BG) are basal progenitors derived from ventricular apical radial glia (aRG) that selectively lose their apical processes. bRG and BG have been implicated in the expansion and folding of the cerebrum and cerebellum, respectively. Here, we analyzed the molecular characteristics and development of bRG and BG. Transcriptomic comparison revealed striking similarity of the molecular features of bRG and BG. We found that heightened ERK signaling activity in aRG is tightly linked to the temporal formation and the relative abundance of bRG in human and mouse cortices. Forced activation of an FGF-ERK-ETV axis that is crucial to BG induction specifically induced bRG with canonical human bRG features in mice. Therefore, our data point to a common mechanism of bRG and BG generation, bearing implications to the role for these basal progenitors in the evolution of cortical folding of the cerebrum and cerebellum.
The epidemiology of homicide-suicide in Italy: a newspaper study from 1985 to 2008.
Forensic science international, 2012

Homicide-suicide is an event in which the murderer commits suicide after the homicide. There are at least 14 epidemiological studies on the topic, and all have found that homicide-suicide is more common among family members. The murderers are most often males and the victims females. There is no recent research on this phenomenon in Italy. The purpose of the study was to evaluate the incidence of homicide-suicide in Italy over a period of 24 yrs and to compare Italian data with published international data. We used information gathered by press agencies and from the four major Italian newspapers. Between 1985 and 2008, 662 cases of homicide-suicide were identified, with 1776 deaths. The murderer was male in 84.6% of the cases, typically using a firearm. The most common motivation was romantic jealousy, followed by socio-economic stress. The rate of homicide-suicide was 0.04%. Comparison with international studies is not always possible due to the lack of information for certain categories. The common factors identified may be helpful for prevention.
The British Neurosurgical Trainee Research Collaborative: Five years on.
Acta neurochirurgica, 2018

Since its inception in 2012, the British Neurosurgical Trainee Research Collaborative (BNTRC) has established itself as a robust example of a trainee-led research collaborative. This article summarises the work of the collaborative over its first 5 years of existence, outlining the structure, its research projects, impact and future directions.