rudyvdbrink/CitationDatabase huggingface dataset:
Dual effects of 5-HT(1a) receptor activation on breathing in neonatal mice.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014

Inhibitory 5-HT(1a) receptors are located on serotonin (5-HT) neurons (autoreceptors) as well as neurons of the respiratory network (heteroreceptors). Thus, effects on breathing of 5-HT(1a) agonists, such as (R)-(+)-8-hydroxy-2-(di-N-propylamino) tetralin (8-OH-DPAT), could either be due to decreased firing of 5-HT neurons or direct effects on the respiratory network. Mice in which the transcription factor LMX1B is genetically deleted selectively in Pet1-1-expressing cells (Lmx1b(f/f/p)) essentially have complete absence of central 5-HT neurons, providing a unique opportunity to separate the effect of activation of downstream 5-HT(1a) heteroreceptors from that of autoreceptors. We used rhythmically active medullary slices from wild-type (WT) and Lmx1b(f/f/p) neonatal mice to differentiate autoreceptor versus heteroreceptor effects of 8-OH-DPAT on hypoglossal nerve respiratory output. 8-OH-DPAT transiently increased respiratory burst frequency in Lmx1b(f/f/p) preparations, but not in WT slices. This excitation was abolished when synaptic inhibition was blocked by GABAergic/glycinergic receptor antagonists. Conversely, after 10 min of application, frequency in Lmx1b(f/f/p) slices was not different from baseline, whereas it was significantly depressed in WT slices. In WT mice in vivo, subcutaneous injection of 8-OH-DPAT produced similar biphasic respiratory effects as in Lmx1b(f/f/p) mice. We conclude that 5-HT1a receptor agonists have two competing effects: rapid stimulation of breathing due to excitation of the respiratory network, and delayed inhibition of breathing due to autoreceptor inhibition of 5-HT neurons. The former effect is presumably due to inhibition of inhibitory interneurons embedded in the respiratory network.
The independence of deficits in position sense and visually guided reaching following stroke.
Journal of neuroengineering and rehabilitation, 2012

Several studies have found correlations between proprioception and visuomotor function during stroke recovery, however two more recent studies have found no correlation. Unfortunately, most of the studies to date have been conducted with clinical assessments of sensation that are observer-based and have poor reliability. We have recently developed new tests to assess position sense and motor function using robotic technology. The present study was conducted to reassess the relationship between position sense and upper limb movement following stroke.
What are frailty instruments for?
Age and ageing, 2015

Frailty is measured to understand its nature and biology, to aid diagnosis and care planning, to measure outcomes and to stratify risk. Such goals oblige two types of frailty measures - for screening and for assessment - and recognition that not all measures will serve all purposes. When the goal is broad identification of people at risk, a dichotomised approach (frailty is present or absent ) is appropriate. If, however, the degree of risk varies, strategies to test grades of frailty will be required. Frailty measures should be implemented and evaluated in relation to the goal for their use.
Mild traumatic brain injuries in adults.
Journal of neurosciences in rural practice, 2010

Mild traumatic brain injury (mTBI) is the commonest form of TBI. Though the name implies, it may not be mild in certain cases. There is a lot of heterogeneity in nomenclature, classification, evaluation and outcome of mTBI. We have reviewed the relevant articles on mTBI in adults, particularly its definition, evaluation and outcome, published in the last decade. The aspects of mTBI like pediatric age group, sports concussion, and postconcussion syndrome were not reviewed. There is general agreement that Glasgow coma score (GCS) of 13 should not be considered as mTBI as the risk of intracranial lesion is higher than in patients with GCS 14-15. All patients with GCS of <15 should be evaluated with a computed tomography (CT) scan. Patients with GCS 15 and risk factors or neurological symptoms should also be evaluated with CT scan. The outcome of mTBI depends on the combination of preinjury, injury and postinjury factors. Overall outcome of mTBI is good with mortality around 0.1% and disability around 10%.
Dock3 induces axonal outgrowth by stimulating membrane recruitment of the WAVE complex.
Proceedings of the National Academy of Sciences of the United States of America, 2010

Atypical Rho-guanine nucleotide exchange factors (Rho-GEFs) that contain Dock homology regions (DHR-1 and DHR-2) are expressed in a variety of tissues; however, their functions and mechanisms of action remain unclear. We identify key conserved amino acids in the DHR-2 domain that are critical for the catalytic activity of Dock-GEFs (Dock1-4). We further demonstrate that Dock-GEFs directly associate with WASP family verprolin-homologous (WAVE) proteins through the DHR-1 domain. Brain-derived neurotrophic factor (BDNF)-TrkB signaling recruits the Dock3/WAVE1 complex to the plasma membrane, whereupon Dock3 activates Rac and dissociates from the WAVE complex in a phosphorylation-dependent manner. BDNF induces axonal sprouting through Dock-dependent Rac activation, and adult transgenic mice overexpressing Dock3 exhibit enhanced optic nerve regeneration after injury without affecting WAVE expression levels. Our results highlight a unique mechanism through which Dock-GEFs achieve spatial and temporal restriction of WAVE signaling, and identify Dock-GEF activity as a potential therapeutic target for axonal regeneration.
Postnatal development of excitatory postsynaptic currents in nucleus accumbens medium spiny neurons.
Neuroscience, 2008

We have recorded excitatory postsynaptic currents (EPSCs) evoked by local electrical stimulation in 243 nucleus accumbens (nAcb) neurons in vitro during postnatal development from the day of birth (postnatal day 0; P0) to P27 and in young adults rats (P59-P71). An EPSC sensitive to glutamatergic antagonists was found in all neurons. In the majority of cases (189/243), the EPSC had two distinct components: an early one sensitive to 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and a late one that was sensitive to D-2-amino-5-phosphonovaleric acid (APV) showing that early and late components of the EPSC were mediated by AMPA/kainate (KA) and N-methyl-D-aspartate (NMDA) receptors respectively. During the first four postnatal days, the amplitudes of both the AMPA/KA and NMDA components of the EPSC were relatively small and then began to increase until the end of the second postnatal week. Whereas the amplitude of the early component appeared to stabilize from that point on, the late component began to decrease and became virtually undetectable in preparations from animals older than 3 weeks unless the AMPA/KA response was blocked with CNQX. In addition, the ratio between the amplitude of the NMDA and AMPA/KA receptor-mediated components of the EPSC followed a developmental pattern parallel to that of the NMDA receptor component showing an increase during the first two postnatal weeks followed by a decrease. Together, these results show that, during postnatal development, there is a period when NMDA receptor-mediated EPSC are preeminent and that time frame might represent a period during which the development of the nAcb might be sensitive to environmental manipulation.
Coupling of NF-protocadherin signaling to axon guidance by cue-induced translation.
Nature neuroscience, 2013

Cell adhesion molecules and diffusible cues both regulate axon pathfinding, yet how these two modes of signaling interact is poorly understood. The homophilic cell adhesion molecule NF-protocadherin (NFPC) is expressed in the mid-dorsal optic tract neuroepithelium and in the axons of developing retinal ganglion cells (RGC) in Xenopus laevis. Here we report that targeted disruption of NFPC function in RGC axons or the optic tract neuroepithelium results in unexpectedly localized pathfinding defects at the caudal turn in the mid-optic tract. Semaphorin 3A (Sema3A), which lies adjacent to this turn, stimulates rapid, protein synthesis-dependent increases in growth cone NFPC and its cofactor, TAF1, in vitro. In vivo, growth cones exhibit marked increases in NFPC translation reporter activity in this mid-optic tract region that are attenuated by blocking neuropilin-1 function. Our results suggest that translation-linked coupling between regionally localized diffusible cues and cell adhesion can help axons navigate discrete segments of the pathway.
Differentiation of two human neuroblastoma cell lines alters SV2 expression patterns.
Cellular & molecular biology letters, 2021

The synaptic vesicle glycoprotein 2 (SV2) family is essential to the synaptic machinery involved in neurotransmission and vesicle recycling. The isoforms SV2A, SV2B and SV2C are implicated in neurological diseases such as epilepsy, Alzheimer's and Parkinson's disease. Suitable cell systems for studying regulation of these proteins are essential. Here we present gene expression data of SV2A, SV2B and SV2C in two human neuroblastoma cell lines after differentiation.
Attention-deficit hyperactivity disorder in adults with epilepsy.
Epilepsy & behavior : E&B, 2019

We investigated the prevalence of attention-deficit hyperactivity disorder (ADHD) in adult people with epilepsy (PWE). We hypothesized that ADHD is common among adult PWE and, some clinical factors may be associated with ADHD.
CaMKII "autonomy" is required for initiating but not for maintaining neuronal long-term information storage.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010

Ca(2+)/calmodulin (CaM)-dependent protein kinase II (CaMKII) "autonomy" (T286-autophosphorylation-induced Ca(2+)-independent activity) is required for long-term potentiation (LTP) and for learning and memory, as demonstrated by CaMKII T286A mutant mice. The >20-year-old hypothesis that CaMKII stimulation is required for LTP induction, while CaMKII autonomy is required for LTP maintenance was recently supported using the cell-penetrating fusion-peptide inhibitor antCN27. However, we demonstrate here that ant/penetratin fusion to CN27 compromised CaMKII-selectivity, by enhancing a previously unnoticed direct binding of CaM to ant/penetratin. In contrast to antCN27, the improved cell-penetrating inhibitor tatCN21 (5 mum) showed neither CaM binding nor inhibition of basal synaptic transmission. In vitro, tatCN21 inhibited stimulated and autonomous CaMKII activity with equal potency. In rat hippocampal slices, tatCN21 inhibited LTP induction, but not LTP maintenance. Correspondingly, tatCN21 also inhibited learning, but not memory storage or retrieval in a mouse in vivo model. Thus, CaMKII autonomy provides a short-term molecular memory that is important in the signal computation leading to memory formation, but is not required as long-term memory store.
The Novel Membrane-Bound Proteins MFSD1 and MFSD3 are Putative SLC Transporters Affected by Altered Nutrient Intake.
Journal of molecular neuroscience : MN, 2017

Membrane-bound solute carriers (SLCs) are essential as they maintain several physiological functions, such as nutrient uptake, ion transport and waste removal. The SLC family comprise about 400 transporters, and we have identified two new putative family members, major facilitator superfamily domain containing 1 (MFSD1) and 3 (MFSD3). They cluster phylogenetically with SLCs of MFS type, and both proteins are conserved in chordates, while MFSD1 is also found in fruit fly. Based on homology modelling, we predict 12 transmembrane regions, a common feature for MFS transporters. The genes are expressed in abundance in mice, with specific protein staining along the plasma membrane in neurons. Depriving mouse embryonic primary cortex cells of amino acids resulted in upregulation of Mfsd1, whereas Mfsd3 is unaltered. Furthermore, in vivo, Mfsd1 and Mfsd3 are downregulated in anterior brain sections in mice subjected to starvation, while upregulated specifically in brainstem. Mfsd3 is also attenuated in cerebellum after starvation. In mice raised on high-fat diet, Mfsd1 was specifically downregulated in brainstem and hypothalamus, while Mfsd3 was reduced consistently throughout the brain.
A 3D ex vivo mandible slice system for longitudinal culturing of transplanted dental pulp progenitor cells.
Cytometry. Part A : the journal of the International Society for Analytical Cytology, 2015

Harnessing mesenchymal stem cells for tissue repair underpins regenerative medicine. However, how the 3D tissue matrix maintains such cells in a quiescent state whilst at the same time primed to respond to tissue damage remains relatively unknown. Developing more physiologically relevant 3D models would allow us to better understand the matrix drivers and influence on cell-lineage differentiation in situ. In this study, we have developed an ex vivo organotypic rat mandible slice model; a technically defined platform for the culture and characterization of dental pulp progenitor cells expressing GFP driven by the β-actin promoter (cGFP DPPCs). Using confocal microscopy we have characterized how the native environment influences the progenitor cells transplanted into the dental pulp. Injected cGFP-DPPCs were highly viable and furthermore differentially proliferated in unique regions of the mandible slice; in the dentine region, cGFP-DPPCs showed a columnar morphology indicative of expansion and lineage differentiation. Hence, we demonstrated the systematic capacity for establishing a dental pulp cell-micro-community, phenotypically modified in the tooth (the "biology"); and at the same time addressed technical challenges enabling the mandible slice to be accessible on platforms for high-content imaging (the biology in a "multiplex" format).
Astrocytes as brain interoceptors.
Experimental physiology, 2011

Astrocytes form a vascular-neuronal interface and provide CNS neural networks with essential structural and metabolic support. They embrace all penetrating arterioles and capillaries, enwrap multiple neuronal somata, thousands of individual synapses, and upon activation release gliotransmitters (ATP, glutamate and D-serine) capable of modulating neuronal activity. The aim of this brief report is to review recent data implicating astrocytes in the brain mechanisms responsible for the detection of different sensory modalities and transmitting sensory information to the relevant neural networks controlling vital behaviours. The concept of astrocytes as brain interoceptors is strongly supported by our recent data obtained from studies of the central nervous mechanisms underlying the chemosensory control of breathing. At the level of the medulla oblongata, astrocytes indeed act as functional central respiratory chemoreceptors, sensing changes in the arterial blood and brain levels of /pH and then imparting these changes on the activity of the respiratory network to induce adaptive changes in lung ventilation.
Maladaptive plasticity, memory for pain and phantom limb pain: review and suggestions for new therapies.
Expert review of neurotherapeutics, 2008

A number of studies have shown that phantom limb pain is associated with plastic changes along the neuraxis, with a close correlation between changes in the cortical representation of the affected limb and phantom limb pain. Mechanisms underlying these maladaptive plastic changes are related to a loss of GABAergic inhibition, glutamate-mediated long-term potentiation-like changes and structural alterations such as axonal sprouting. These plastic changes and phantom limb pain seem to be more extensive when chronic pain precedes the amputation. Behavioral interventions, stimulation, feedback and pharmacological interventions that are designed to reverse these maladaptive memory traces and enhance extinction may be beneficial for the treatment and prevention of phantom limb pain.
Thomas Willis of the "circle of Willis".
Neurosurgery, 2008

Thomas Willis is best known for the circle of Willis. The life story of this 17th- century medical genius, who remains an inspiration for all neuroscientists 300 years later, is summarized in this article. We outline his academic achievements, including his description of the famous basal arterial circle, and we attempt to obtain insight into his visionary thought process through this historical review.
Taking advantage of the systemic immune system to cure brain diseases.
Neuron, 2009

The systemic immune system has the ability to modulate multiple brain functions, including autonomic responses, glial reactivity following neural injuries, and neuronal excitability. Immune stimuli also influence microglia subpopulations originating from blood progenitors, and neuroprotective and reparative capacities of blood-derived microglia were recently described in mouse models of spinal cord injury and brain disorders. Furthermore, reparative roles for various immune subsets have been recognized, such as in inducing myelin repair. Nonetheless, uncontrolled and excessive activation of immune responses can be detrimental. The development of strategies to stimulate the systemic immune system safely to protect or repair brain disorders remains a major challenge ahead, but important inroads have been made. We discuss here some of the mechanisms underlying the neuroprotective and reparative effects of the systemic immune system and the most promising immunotherapies tested in mouse models of injuries and diseases, such as Alzheimer's disease, amyotrophic lateral sclerosis, and multiple sclerosis.
Vasoreactivity in CADASIL: Comparison to structural MRI and neuropsychology.
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2018

Impaired cerebrovascular reactivity precedes histological and clinical evidence of CADASIL in animal models. We aimed to more fully characterise peripheral and cerebral vascular function and reactivity in a cohort of adult CADASIL patients, and explore the associations of these with conventional clinical, imaging and neuropsychological measures. A total of 22 adults with CADASIL gave informed consent to participate in an exploratory study of vascular function in CADASIL. Clinical assessment, comprehensive vascular assessment, MRI and neuropsychological testing were conducted. We measured cerebral vasoreactivity with transcranial Doppler and arterial spin labelling MRI with hypercapnia challenge. Number and volume of lacunes, subcortical hyperintensity volume, microbleeds and normalised brain volume were assessed on MRI. Analysis was exploratory and examined the associations between different markers. Cerebrovascular reactivity measured by ASL correlated with peripheral vasoreactivity measured by flow mediated dilatation. Subjects with ≥5 lacunes were older, with higher carotid intima-media thickness and had impaired cerebral and peripheral vasoreactivity. Subjects with depressive symptoms, disability or delayed processing speed also showed a trend to impaired vasoreactivity. Impaired vasoreactivity and vascular dysfunction may play a significant role in the pathophysiology of CADASIL, and vascular assessments may be useful biomarkers of severity in both longitudinal and clinical trials.
TrkB signaling is required for both the induction and maintenance of tissue and nerve injury-induced persistent pain.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2009

Activation of primary afferent nociceptors produces acute, short-lived pain, and tissue or nerve injury induces long-term enhancement of nociceptive processing, manifested as hypersensitivity to thermal and mechanical stimulation. Here we used a chemical-genetic and pharmacological approach to study the contribution of the receptor tyrosine kinase, type 2 (TrkB) to the generation and maintenance of injury-induced persistent pain. We performed the studies in wild-type mice and transgenic (TrkB(F616A)) mice that express mutant but fully functional TrkB receptors. By injecting a small molecule derivative of the protein kinase inhibitor protein phosphatase 1 (1NM-PP1), it is possible to produce highly selective inhibition of TrkB autophosphorylation in adult mice, without interfering with the activity of other protein kinases. We report that oral administration of 1NM-PP1, at doses that blocked phosphorylation of TrkB in the spinal cord, had no effect in behavioral tests of acute heat, mechanical, or chemical pain sensitivity. However, the same pretreatment with 1NM-PP1 prevented the development of tissue- or nerve injury-induced heat and mechanical hypersensitivity. Established hypersensitivity was transiently reversed by intraperitoneal injection of 1NM-PP1. Although interfering with TrkB signaling altered neither acute capsaicin nor formalin-induced pain behavior, the prolonged mechanical hypersensitivity produced by these chemical injuries was prevented by 1NM-PP1 inhibition of TrkB signaling. We conclude that TrkB signaling is not only an important contributor to the induction of heat and mechanical hypersensitivity produced by tissue or nerve injury but also to the persistence of the pain.
Intraventricular fibrinolysis versus external ventricular drainage alone in intraventricular hemorrhage: a meta-analysis.
Stroke, 2011

The purpose of this study was to analyze the effect of intraventricular fibrinolysis (IVF) compared with external ventricular drainage alone on mortality and functional outcome in the management of intraventricular hemorrhage secondary to spontaneous supratentorial intracerebral hemorrhage.
A new biophysical decompression model for estimating the risk of articular bends during and after decompression.
Journal of theoretical biology, 2011

The biophysical models that intend to predict the risk of decompression sickness after a change of pressure are not numerous. Few approaches focus in particular on joints as target tissues, with the aim to describe properly the mechanisms inducing pain. Nevertheless, for this type of decompression incidents, called articular bends, no model proved to fit the empirical results for a broad range of exposures and decompression procedures. We present here an original biophysical decompression model for describing the occurrence of articular bends. A target joint is broken down into two parts that exchange inert gases with the blood by perfusion and with each other by diffusion over distances of a few millimetres. This diffusion pathway allows the slow amplification of microbubbles growing during and after decompression, consistent with the possible delayed occurrence of bends. The diffusion coefficients introduced into this model are larger than those introduced into most modern decompression models. Their value remains physical (#10(-9)m(2)/s). Inert gas exchanges and the formation, amplification and resorption of microbubbles during and after decompression were simulated. We used a critical gas volume criterion for predicting the occurrence of bends. A risk database extracted from COMEX experience and other published studies were used for the correlation of model parameters not known a priori. We considered a large range of exposure, and the commonly used inert gases nitrogen and helium. This correlation phase identified the worst biophysical conformations most likely to lead to the formation, in tissues such as tendons, of a large number of microbubbles recruited from pre-existing gas nuclei during decompression. The risk of bends occurrence was found to be linked to the total separated gas volume generated during and after decompression. A clamping phenomenon occurs soon after the start of decompression, greatly slowing the gas exchanges controlled especially by the oxygen window. This model, which reproduces many empirical findings, may be considered both descriptive and predictive.