rudyvdbrink/CitationDatabase huggingface dataset:
Axotomy of tributaries of the pelvic and pudendal nerves induces changes in the neurochemistry of mouse dorsal root ganglion neurons and the spinal cord.
Brain structure & function, 2016

Using immunohistochemical techniques, we characterized changes in the expression of several neurochemical markers in lumbar 4-sacral 2 (L4-S2) dorsal root ganglion (DRG) neuron profiles (NPs) and the spinal cord of BALB/c mice after axotomy of the L6 and S1 spinal nerves, major tributaries of the pelvic (targeting pelvic visceral organs) and pudendal (targeting perineum and genitalia) nerves. Sham animals were included. Expression of cyclic AMP-dependent transcription factor 3 (ATF3), calcitonin gene-related peptide (CGRP), transient receptor potential cation channel subfamily V, member 1 (TRPV1), tyrosine hydroxylase (TH) and vesicular glutamate transporters (VGLUT) types 1 and -2 was analysed seven days after injury. L6-S1 axotomy induced dramatic de novo expression of ATF3 in many L6-S1 DRG NPs, and parallel significant downregulations in the percentage of CGRP-, TRPV1-, TH- and VGLUT2-immunoreactive (IR) DRG NPs, as compared to their expression in uninjured DRGs (contralateral L6-S1-AXO; sham mice); VGLUT1 expression remained unaltered. Sham L6-S1 DRGs only showed a small ipsilateral increase in ATF3-IR NPs (other markers were unchanged). L6-S1-AXO induced de novo expression of ATF3 in several lumbosacral spinal cord motoneurons and parasympathetic preganglionic neurons; in sham mice the effect was limited to a few motoneurons. Finally, a moderate decrease in CGRP- and TRPV1-like-immunoreactivities was observed in the ipsilateral superficial dorsal horn neuropil. In conclusion, injury of a mixed visceral/non-visceral nerve leads to considerable neurochemical alterations in DRGs matched, to some extent, in the spinal cord. Changes in these and potentially other nociception-related molecules could contribute to pain due to injury of nerves in the abdominopelvic cavity.
Opposing effects of an F-box protein and the HSP90 chaperone network on microtubule stability and neurite growth in 
Development (Cambridge, England), 2020

Molecular chaperones often work collaboratively with the ubiquitylation-proteasome system (UPS) to facilitate the degradation of misfolded proteins, which typically safeguards cellular differentiation and protects cells from stress. In this study, however, we report that the Hsp70/Hsp90 chaperone machinery and an F-box protein, MEC-15, have opposing effects on neuronal differentiation, and that the chaperones negatively regulate neuronal morphogenesis and functions. Using the touch receptor neurons (TRNs) of
Novel selective allosteric activator of the M1 muscarinic acetylcholine receptor regulates amyloid processing and produces antipsychotic-like activity in rats.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2008

Recent studies suggest that subtype-selective activators of M(1)/M(4) muscarinic acetylcholine receptors (mAChRs) may offer a novel approach for the treatment of psychotic symptoms associated with schizophrenia and Alzheimer's disease. Previously developed muscarinic agonists have provided clinical data in support of this hypothesis, but failed in clinical development because of a lack of true subtype specificity and adverse effects associated with activation of other mAChR subtypes. We now report characterization of a novel highly selective agonist for the M(1) receptor with no agonist activity at any of the other mAChR subtypes, termed TBPB [1-(1'-2-methylbenzyl)-1,4'-bipiperidin-4-yl)-1H-benzo[d]imidazol-2(3H)-one]. Mutagenesis and molecular pharmacology studies revealed that TBPB activates M(1) through an allosteric site rather than the orthosteric acetylcholine binding site, which is likely critical for its unprecedented selectivity. Whole-cell patch-clamp recordings demonstrated that activation of M(1) by TBPB potentiates NMDA receptor currents in hippocampal pyramidal cells but does not alter excitatory or inhibitory synaptic transmission, responses thought to be mediated by M(2) and M(4). TBPB was efficacious in models predictive of antipsychotic-like activity in rats at doses that did not produce catalepsy or peripheral adverse effects of other mAChR agonists. Finally, TBPB had effects on the processing of the amyloid precursor protein toward the non-amyloidogenic pathway and decreased Abeta production in vitro. Together, these data suggest that selective activation of M(1) may provide a novel approach for the treatment of symptoms associated with schizophrenia and Alzheimer's disease.
Molecular determinants controlling NMDA receptor synaptic incorporation.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011

Synaptic incorporation of NMDA receptors (NMDARs) is regulated by GluN2 subunits with different rules controlling GluN2A- and GluN2B-containing receptors; whereas GluN2B-containing receptors are constitutively incorporated into synapses, GluN2A incorporation is activity-dependent. We expressed electrophysiologically tagged NMDARs in rat hippocampal slices to identify the molecular determinants controlling the mode of synaptic incorporation of NMDARs. Expressing chimeric GluN2 subunits, we identified a putative N-glycosylation site present in GluN2B, but not in GluN2A, as necessary and sufficient to drive NMDARs into synapses in an activity-independent manner. This suggests a novel mechanism for regulating activity-driven changes and trafficking of NMDARs to the synapse.
Brief, intensive and concentrated cognitive behavioral treatments for anxiety disorders in children: A systematic review and meta-analysis.
Behaviour research and therapy, 2017

Anxiety disorders are among the most common disorders affecting youths in the general population, with up to 10% of children and 20% of adolescents meeting criteria for an anxiety disorder at any one point in time. Cognitive-behavior therapies (CBT), varying between 9 and 18 weeks of treatment, are considered evidence-based for the treatment of anxiety disorders in youth. During the last two decades treatments that are brief, intensive, or concentrated (BIC) have been developed and this meta-analysis includes 23 RCTs of these new approaches across the anxiety disorders. BIC yielded a lower attrition (2.3%) than standard CBT (6.5%). The effect sizes (ES) for comparison of BIC with waiting-list (1.47) and placebo (0.91) were significant, whereas that with standard CBT (0.01) was not. Regarding remission at post/recovery at follow-up BIC (54%/64%) and standard CBT (57%/63%) were comparable and both were significantly higher than placebo (26%/35%), which was higher than WLC (7%/9%). Within-group ES at post and follow-up were 1.50 and 1.53 for BIC, and 0.98 and 1.05 for standard CBT, indicating maintenance of the effects up to 12 months after therapy. Advantages and disadvantages of BIC are discussed and we suggest that BIC-interventions represent a paradigm shift in the delivery of services for youth with anxiety disorders.
Dopamine depletion shifts behavior from activity based reinforcers to more sedentary ones and adenosine receptor antagonism reverses that shift: Relation to ventral striatum DARPP32 phosphorylation patterns.
Neuropharmacology, 2018

The mesolimbic dopamine (DA) system plays a critical role in behavioral activation and effort-based decision-making. DA depletion produces anergia (shifts to low effort options) in animals tested on effort-based decision-making tasks. Caffeine, the most consumed stimulant in the world, acts as an adenosine A
Exploring venlafaxine pharmacokinetic variability with a phenotyping approach, a multicentric french-swiss study (MARVEL study).
BMC pharmacology & toxicology, 2017

It is well known that the standard doses of a given drug may not have equivalent effects in all patients. To date, the management of depression remains mainly empirical and often poorly evaluated. The development of a personalized medicine in psychiatry may reduce treatment failure, intolerance or resistance, and hence the burden and costs of mood depressive disorders. The Geneva Cocktail Phenotypic approach presents several advantages including the "in vivo" measure of different cytochromes and transporter P-gp activities, their simultaneous determination in a single test, avoiding the influence of variability over time on phenotyping results, the administration of low dose substrates, a limited sampling strategy with an analytical method developed on DBS analysis. The goal of this project is to explore the relationship between the activity of drug-metabolizing enzymes (DME), assessed by a phenotypic approach, and the concentrations of Venlafaxine (VLX) + O-demethyl-venlafaxine (ODV), the efficacy and tolerance of VLX.
Spatially 2D-selective RF excitations using the PROPELLER trajectory: basic principles and application to MR spectroscopy of irregularly shaped single voxel.
Magnetic resonance in medicine, 2011

Spatially two-dimensional selective radio frequency (2DRF) excitations are able to excite arbitrarily-shaped profiles in their excitation plane and, hence, can be used to minimize partial volume effects in single-voxel magnetic resonance spectroscopy. In this study, 2DRF excitations based on the PROPELLER trajectory which consists of blades of parallel lines that are rotated against each other, are presented. Because the k-space center is covered with each segment, the trajectory yields a high signal efficiency which, e.g., is considerably improved compared to a segmented blipped-planar approach. It is shown that a sampling density correction based on the PROPELLER trajectory's Voronoi diagram suppresses unwanted side excitations. Off-resonance effects like chemical-shift displacement artifacts, can be minimized by applying nonselective refocusing radio frequency pulses between the lines of a blade. With half-Fourier segments, the 2DRF's echo time contribution can be shortened considerably. Thus, robust 2DRF excitations capable of exciting high-resolution profiles at short echo times with high signal efficiency are obtained. Their applicability to MR spectroscopy of an arbitrarily-shaped single voxel is demonstrated in a two-bottle phantom and in the human brain in vivo on a 3 T whole-body MR system.
Natural products and phytochemical nanoformulations targeting mitochondria in oncotherapy: an updated review on resveratrol.
Bioscience reports, 2020

Mitochondria are intracellular organelles with two distinct membranes, known as an outer mitochondrial membrane and inner cell membrane. Originally, mitochondria have been derived from bacteria. The main function of mitochondria is the production of ATP. However, this important organelle indirectly protects cells by consuming oxygen in the route of energy generation. It has been found that mitochondria are actively involved in the induction of the intrinsic pathways of apoptosis. So, there have been efforts to sustain mitochondrial homeostasis and inhibit its dysfunction. Notably, due to the potential role of mitochondria in the stimulation of apoptosis, this organelle is a promising target in cancer therapy. Resveratrol is a non-flavonoid polyphenol that exhibits significant pharmacological effects such as antioxidant, anti-diabetic, anti-inflammatory and anti-tumor. The anti-tumor activity of resveratrol may be a consequence of its effect on mitochondria. Multiple studies have investigated the relationship between resveratrol and mitochondria, and it has been demonstrated that resveratrol is able to significantly enhance the concentration of reactive oxygen species, leading to the mitochondrial dysfunction and consequently, apoptosis induction. A number of signaling pathways such as sirtuin and NF-κB may contribute to the mitochondrial-mediated apoptosis by resveratrol. Besides, resveratrol shifts cellular metabolism from glycolysis into mitochondrial respiration to induce cellular death in cancer cells. In the present review, we discuss the possible interactions between resveratrol and mitochondria, and its potential application in cancer therapy.
Inhibitory effect of estrogen receptor beta on P2X3 receptors during inflammation in rats.
Purinergic signalling, 2017

Estrogen receptor beta (ERβ) has been shown to play a therapeutic role in inflammatory bowel disease (IBD). However, the mechanism underlying how ERβ exerts therapeutic effects and its relationship with P2X3 receptors (P2X3R) in rats with inflammation is not known. In our study, animal behavior tests, visceromotor reflex recording, and Western blotting were used to determine whether the therapeutic effect of ERβ in rats with inflammation was related with P2X3R. In complete Freund adjuvant (CFA)-induced chronic inflammation in rats, paw withdrawal threshold was significantly decreased which were then reversed by systemic injection of ERβ agonists, DPN or ERB-041. In 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats, weight loss, higher DAI scores, increased visceromotor responses, and inflammatory responses were reversed by application of DPN or ERB-041. The higher expressions of P2X3R in dorsal root ganglia (DRG) of CFA-treated rats and those in rectocolon and DRG of TNBS-treated rats were all decreased by injection of DPN or ERB-041. DPN application also inhibited P2X3R-evoked inward currents in DRG neurons from TNBS rats. Mechanical hyperalgesia and increased P2X3 expression in ovariectomized (OVX) CFA-treated rats were reversed by estrogen replacements. Furthermore, the expressions of extracellular signal-regulated kinase (ERK) in DRG and spinal cord dorsal horn (SCDH) and c-fos in SCDH were significantly decreased after estrogen replacement compared with those of OVX rats. The ERK antagonist U0126 significantly reversed mechanical hyperalgesia in the OVX rats. These results suggest that estrogen may play an important therapeutic role in inflammation through down-regulation of P2X3R in peripheral tissues and the nervous system, probably via ERβ, suggesting a novel therapeutic strategy for clinical treatment of inflammation.
Increased oxidative stress in the mitochondria isolated from lymphocytes of bipolar disorder patients during depressive episodes.
Psychiatry research, 2018

The present study aims to investigate the oxidative stress parameters in isolated mitochondria, as well as looking at mitochondrial complex activity in patients with Bipolar Disorder (BD) during depressive or euthymic episodes. This study evaluated the levels of mitochondrial complex (I, II, II-III and IV) activity in lymphocytes from BD patients. We evaluated the following oxidative stress parameters: superoxide, thiobarbituric acid reactive species (TBARS) and carbonyl levels in submitochondrial particles of lymphocytes from bipolar patients. 51 bipolar patients were recruited into this study: 34 in the euthymic phase, and 17 in the depressive phase. Our results indicated that the depressive phase could increase the levels of mitochondrial superoxide, carbonyl and TBARS, and superoxide dismutase, and could decrease the levels of mitochondrial complex II activity in the lymphocytes of bipolar patients. It was also observed that there was a negative correlation between the Hamilton Depression Rating Scale (HDRS) and complex II activity in the lymphocytes of depressive bipolar patients. In addition, there was a positive correlation between HDRS and superoxide, superoxide dismutase, TBARS and carbonyl. Additionally, there was a negative correlation between complex II activity and oxidative stress parameters. In conclusion, our results suggest that mitochondrial oxidative stress and mitochondrial complex II dysfunction play important roles in the depressive phase of BD.
Altered functional connectivity and performance variability in relapsing-remitting multiple sclerosis.
Multiple sclerosis (Houndmills, Basingstoke, England), 2014

Patients with multiple sclerosis (MS) demonstrate slower and more variable performance on attention and information processing speed tasks. Greater variability in cognitive task performance has been shown to be an important predictor of neurologic status and provides a unique measure of cognitive performance in MS patients.
REM-Enriched Naps Are Associated with Memory Consolidation for Sad Stories and Enhance Mood-Related Reactivity.
Brain sciences, 2015

Emerging evidence suggests that emotion and affect modulate the relation between sleep and cognition. In the present study, we investigated the role of rapid-eye movement (REM) sleep in mood regulation and memory consolidation for sad stories. In a counterbalanced design, participants (n = 24) listened to either a neutral or a sad story during two sessions, spaced one week apart. After listening to the story, half of the participants had a short (45 min) morning nap. The other half had a long (90 min) morning nap, richer in REM and N2 sleep. Story recall, mood evolution and changes in emotional response to the re-exposure to the story were assessed after the nap. Although recall performance was similar for sad and neutral stories irrespective of nap duration, sleep measures were correlated with recall performance in the sad story condition only. After the long nap, REM sleep density positively correlated with retrieval performance, while re-exposure to the sad story led to diminished mood and increased skin conductance levels. Our results suggest that REM sleep may not only be associated with the consolidation of intrinsically sad material, but also enhances mood reactivity, at least on the short term.
Neuronal selectivity to complex vocalization features emerges in the superficial layers of primary auditory cortex.
PLoS biology, 2021

Early in auditory processing, neural responses faithfully reflect acoustic input. At higher stages of auditory processing, however, neurons become selective for particular call types, eventually leading to specialized regions of cortex that preferentially process calls at the highest auditory processing stages. We previously proposed that an intermediate step in how nonselective responses are transformed into call-selective responses is the detection of informative call features. But how neural selectivity for informative call features emerges from nonselective inputs, whether feature selectivity gradually emerges over the processing hierarchy, and how stimulus information is represented in nonselective and feature-selective populations remain open question. In this study, using unanesthetized guinea pigs (GPs), a highly vocal and social rodent, as an animal model, we characterized the neural representation of calls in 3 auditory processing stages-the thalamus (ventral medial geniculate body (vMGB)), and thalamorecipient (L4) and superficial layers (L2/3) of primary auditory cortex (A1). We found that neurons in vMGB and A1 L4 did not exhibit call-selective responses and responded throughout the call durations. However, A1 L2/3 neurons showed high call selectivity with about a third of neurons responding to only 1 or 2 call types. These A1 L2/3 neurons only responded to restricted portions of calls suggesting that they were highly selective for call features. Receptive fields of these A1 L2/3 neurons showed complex spectrotemporal structures that could underlie their high call feature selectivity. Information theoretic analysis revealed that in A1 L4, stimulus information was distributed over the population and was spread out over the call durations. In contrast, in A1 L2/3, individual neurons showed brief bursts of high stimulus-specific information and conveyed high levels of information per spike. These data demonstrate that a transformation in the neural representation of calls occurs between A1 L4 and A1 L2/3, leading to the emergence of a feature-based representation of calls in A1 L2/3. Our data thus suggest that observed cortical specializations for call processing emerge in A1 and set the stage for further mechanistic studies.
Primary tissue for cellular brain repair in Parkinson's disease: Promise, problems and the potential of biomaterials.
The European journal of neuroscience, 2019

The dopamine precursor, levodopa, remains the "gold standard" treatment for Parkinson's disease, and, although it provides superlative efficacy in the early stages of the disease, its long-term use is limited by the development of severe motor side effects and a significant abating of therapeutic efficacy. Therefore, there remains a major unmet clinical need for the development of effective neuroprotective, neurorestorative or neuroreparatory therapies for this condition. The relatively selective loss of dopaminergic neurons from the nigrostriatal pathway makes Parkinson's disease an ideal candidate for reparative cell therapies, wherein the dopaminergic neurons that are lost in the condition are replaced through direct cell transplantation into the brain. To date, this approach has been developed, validated and clinically assessed using dopamine neuron-rich foetal ventral mesencephalon grafts which have been shown to survive and reinnervate the denervated brain after transplantation, and to restore motor function. However, despite long-term symptomatic relief in some patients, significant limitations, including poor graft survival and the impact this has on the number of foetal donors required, have prevented this therapy being more widely adopted as a restorative approach for Parkinson's disease. Injectable biomaterial scaffolds have the potential to improve the delivery, engraftment and survival of these grafts in the brain through provision of a supportive microenvironment for cell adhesion, growth and immune shielding. This article will briefly review the development of primary cell therapies for brain repair in Parkinson's disease and will consider the emerging literature which highlights the potential of using injectable biomaterial hydrogels in this context.
Autism is associated with reduced ability to interpret grasping actions of others.
Scientific reports, 2017

We investigated the ability of children with ASD to discriminate a small cylinder from a large cube by observing a point-light movie of an actor grasping the object, either from an allocentric or egocentric viewpoint (observing action of others or self). Compared with typically developing controls, high functioning autistic children showed a strong selective impairment in this task, but only with the allocentric viewpoint, where thresholds were twice as high: egocentric thresholds were similar to age- and ability-matched controls. The magnitude of the impairment correlated strongly with the degree of symptomology (R