rudyvdbrink/CitationDatabase huggingface dataset:
AdipoRon Attenuates Neuroinflammation After Intracerebral Hemorrhage Through AdipoR1-AMPK Pathway.
Neuroscience, 2019

Neuroinflammation is considered to be a critical component in the pathological process after intracerebral hemorrhage (ICH). Microglia are the foremost and earliest inflammatory cells participating in the pathological process of ICH. AdipoRon is the agonist of AdipoR1 (Adiponectin receptor 1), which enhances P-AMPK (phosphorylated AMP-activated protein kinase) activation. The activated AMPK facilitates microglia/macrophage polarization by driving the cell state from pro-inflammatory M1 state to anti-inflammatory M2 state. The study aims to investigate the role of AdipoRon in microglial polarization and neuroprotection after ICH. The experimental ICH model was established by autologous blood injection, and the treated group was done additionally by intraperitoneal injection of drugs. Flow cytometry analysis and immunofluorescence staining were performed to quantify the ratio of M1 to M2 phenotype microglia in mice. The present study indicated that AdipoRon could ameliorate neurological deficits in mice after ICH. Flow cytometric analysis demonstrated that the proportion of CD206
Short latency cerebellar modulation of the basal ganglia.
Nature neuroscience, 2014

The graceful, purposeful motion of our body is an engineering feat that remains unparalleled in robotic devices using advanced artificial intelligence. Much of the information required for complex movements is generated by the cerebellum and the basal ganglia in conjunction with the cortex. Cerebellum and basal ganglia have been thought to communicate with each other only through slow, multi-synaptic cortical loops, begging the question as to how they coordinate their outputs in real time. We found that the cerebellum rapidly modulates the activity of the striatum via a disynaptic pathway in mice. Under physiological conditions, this short latency pathway was capable of facilitating optimal motor control by allowing the basal ganglia to incorporate time-sensitive cerebellar information and by guiding the sign of cortico-striatal plasticity. Conversely, under pathological condition, this pathway relayed aberrant cerebellar activity to the basal ganglia to cause dystonia.
Sox1a mediates the ability of the parapineal to impart habenular left-right asymmetry.
eLife, 2019

Left-right asymmetries in the zebrafish habenular nuclei are dependent upon the formation of the parapineal, a unilateral group of neurons that arise from the medially positioned pineal complex. In this study, we show that both the left and right habenula are competent to adopt left-type molecular character and efferent connectivity upon the presence of only a few parapineal cells. This ability to impart left-sided character is lost in parapineal cells lacking Sox1a function, despite the normal specification of the parapineal itself. Precisely timed laser ablation experiments demonstrate that the parapineal influences neurogenesis in the left habenula at early developmental stages as well as neurotransmitter phenotype and efferent connectivity during subsequent stages of habenular differentiation. These results reveal a tight coordination between the formation of the unilateral parapineal nucleus and emergence of asymmetric habenulae, ensuring that appropriate lateralised character is propagated within left and right-sided circuitry.
Cortical excitation and inhibition following focal traumatic brain injury.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011

Cortical compression can be a significant problem in many types of brain injuries, such as brain trauma, localized brain edema, hematoma, focal cerebral ischemia, or brain tumors. Mechanical and cellular alterations can result in global changes in excitation and inhibition on the neuronal network level even in the absence of histologically significant cell injury, often manifesting clinically as seizures. Despite the importance and prevalence of this problem, however, the precise electrophysiological effects of brain injury have not been well characterized. In this study, the changes in electrophysiology were characterized following sustained cortical compression using large-scale, multielectrode measurement of multiunit activity in primary somatosensory cortex in a sensory-evoked, in vivo animal model. Immediately following the initiation of injury at a distal site, there was a period of suppression of the evoked response in the rat somatosensory cortex, followed by hyper-excitability that was accompanied by an increase in the spatial extent of cortical activation. Paired-pulse tactile stimulation revealed a dramatic shift in the excitatory/inhibitory dynamics, suggesting a longer term hyperexcitability of the cortical circuit following the initial suppression that could be linked to the disruption of one or more inhibitory mechanisms of the thalamocortical circuit. Together, our results showed that the use of a sensory-evoked response provided a robust and repeatable functional marker of the evolution of the consequences of mild injury, serving as an important step toward in vivo quantification of alterations in excitation and inhibition in the cortex in the setting of traumatic brain injury.
Cell-type identity: a key to unlocking the function of neocortical circuits.
Current opinion in neurobiology, 2009

A central tenet of neuroscience is that the precise patterns of connectivity among neurons in a given brain area underlie its function. However, assigning any aspect of perception or behavior to the wiring of local circuits has been challenging. Here, we review recent work in sensory neocortex that demonstrates the power of identifying specific cell types when investigating the functional organization of brain circuits. These studies indicate that knowing the identity of both the presynaptic and postsynaptic cell type is key when analyzing neocortical circuits. Furthermore, identifying the circuit organization of particular cell types in the neocortex allows the recording and manipulation of each cell type's activity and the direct testing of its functional role in perception and behavior.
Adverse effects of methylene blue on the central nervous system.
Anesthesiology, 2008

An increasing number of clinical observations suggest adverse neurologic outcome after methylene blue (MB) infusion in the setting of parathyroid surgery. Hence, the aim of the current study was to investigate the potentially neurotoxic effects of MB using a combination of in vivo and in vitro experimental approaches.
Long-term administration of cocaine or serotonin reuptake inhibitors results in anatomical and neurochemical changes in noradrenergic, dopaminergic, and serotonin pathways.
Journal of neurochemistry, 2008

The catechol and indole pathways are important components underlying plasticity in the frontal cortex and basal ganglia. This study demonstrates that administering rats either cocaine or a selective serotonin (or 5-hydroxytryptamine; 5-HT) reuptake inhibitor (SSRI) for 16 weeks results in reduced density of dopaminergic and noradrenergic terminals in the striatum and olfactory bulb, respectively, reflecting pruning of the terminal arbor of ventral midbrain dopaminergic and locus coeruleus noradrenergic neurones. In the striatum of cocaine-treated animals, basal dopamine levels, as well as cocaine-induced dopamine release, is diminished compared with controls. In contrast, serotonergic fibers, projecting from the raphe, sprout and have increased terminal density in the lateral septal nucleus and frontal cortex, following long-term cocaine or SSRI treatment. This is associated with elevated basal 5-HT and enhanced cocaine-induced 5-HT release in the frontal cortex. The anatomical and neurochemical changes in serotonergic fibers following cocaine or SSRI treatment may be explained by attenuated 5-HT(1A) autoreceptor function in the raphe. This study demonstrates extensive plasticity in the morphology and neurochemistry of the catechol and indole pathways that contribute to drug-induced plasticity of the corticostriatal (and other) projections. Moreover, our data suggest that drug-induced plastic adaptation is anatomically widespread and consequently, likely to have multiple and complex consequences.
Comparison of cognitive function between early- and late-onset late-life depression in remission.
Psychiatry research, 2020

Differences in cognitive function have been suggested in people with late-life depression between those with early- (EOD) and late-onset (LOD), possibly reflecting different etiologies. The cutoff point for EOD and LOD was the first depressive episode before age 60 or later. However, depressive symptoms at the time of disorder are important confounders. The study aimed to compare cognitive function in older people with EOD and LOD in the euthymic state. A sample of 135 participants aged 60+ with a history of major depressive disorder in remission, received neuropsychological evaluation including tests of memory, attention, processing speed, visuospatial function, language, and executive function. Individual test scores and a derived composite score were investigated as dependent variables against age of onset using multiple linear regressions adjusted for potential confounders, including residual depressive symptoms. We found EOD (N = 67) and LOD (N = 68) groups did not differ significantly in overall composite cognitive scores after adjustment. Of individual test scores, only those for immediate recall were significantly lower in participants with EOD compared to LOD. In conclusion, the study found no associations between cognitive function and age of onset in this sample of people with depressive disorder in remission. Active or residual depressive symptoms might have confounded this relationship in previous research.
Single-Particle Diffusion Characterization by Deep Learning.
Biophysical journal, 2019

Diffusion plays a crucial role in many biological processes including signaling, cellular organization, transport mechanisms, and more. Direct observation of molecular movement by single-particle-tracking experiments has contributed to a growing body of evidence that many cellular systems do not exhibit classical Brownian motion but rather anomalous diffusion. Despite this evidence, characterization of the physical process underlying anomalous diffusion remains a challenging problem for several reasons. First, different physical processes can exist simultaneously in a system. Second, commonly used tools for distinguishing between these processes are based on asymptotic behavior, which is experimentally inaccessible in most cases. Finally, an accurate analysis of the diffusion model requires the calculation of many observables because different transport modes can result in the same diffusion power-law α, which is typically obtained from the mean-square displacements (MSDs). The outstanding challenge in the field is to develop a method to extract an accurate assessment of the diffusion process using many short trajectories with a simple scheme that is applicable at the nonexpert level. Here, we use deep learning to infer the underlying process resulting in anomalous diffusion. We implement a neural network to classify single-particle trajectories by diffusion type: Brownian motion, fractional Brownian motion and continuous time random walk. Further, we demonstrate the applicability of our network architecture for estimating the Hurst exponent for fractional Brownian motion and the diffusion coefficient for Brownian motion on both simulated and experimental data. These networks achieve greater accuracy than time-averaged MSD analysis on simulated trajectories while only requiring as few as 25 steps. When tested on experimental data, both net and ensemble MSD analysis converge to similar values; however, the net needs only half the number of trajectories required for ensemble MSD to achieve the same confidence interval. Finally, we extract diffusion parameters from multiple extremely short trajectories (10 steps) using our approach.
Auditory nerve inputs to cochlear nucleus neurons studied with cross-correlation.
Neuroscience, 2008

The strength of synapses between auditory nerve (AN) fibers and ventral cochlear nucleus (VCN) neurons is an important factor in determining the nature of neural integration in VCN neurons of different response types. Synaptic strength was analyzed using cross-correlation of spike trains recorded simultaneously from an AN fiber and a VCN neuron in anesthetized cats. VCN neurons were classified as chopper, primarylike, and onset using previously defined criteria, although onset neurons usually were not analyzed because of their low discharge rates. The correlograms showed an excitatory peak (EP), consistent with monosynaptic excitation, in AN-VCN pairs with similar best frequencies (49% 24/49 of pairs with best frequencies within +/-5%). Chopper and primarylike neurons showed similar EPs, except that the primarylike neurons had shorter latencies and shorter-duration EPs. Large EPs consistent with end bulb terminals on spherical bushy cells were not observed, probably because of the low probability of recording from one. The small EPs observed in primarylike neurons, presumably spherical bushy cells, could be derived from small terminals that accompany end bulbs on these cells. EPs on chopper or primarylike-with-notch neurons were consistent with the smaller synaptic terminals on multipolar and globular bushy cells. Unexpectedly, EPs were observed only at sound levels within about 20 dB of threshold, showing that VCN responses to steady tones shift from a 1:1 relationship between AN and VCN spikes at low sound levels to a more autonomous mode of firing at high levels. In the high level mode, the pattern of output spikes seems to be determined by the properties of the postsynaptic spike generator rather than the input spike patterns. The EP amplitudes did not change significantly when the presynaptic spike was preceded by either a short or long interspike interval, suggesting that synaptic depression and facilitation have little effect under the conditions studied here.
Improvements in rate of development and magnitude of force with intense auditory stimuli in patients with Parkinson's disease.
The European journal of neuroscience, 2011

Patients with Parkinson's disease can show brief but dramatic normalization of motor activity in highly arousing situations, a phenomenon often termed paradoxical kinesis. We sought to mimic this in a controlled experimental environment. Nine patients with Parkinson's disease and nine age-matched healthy controls were asked to grip a force dynamometer as quickly and strongly as possible in response to a visual cue. A loud (96 dB) auditory stimulus was delivered at the same time as the visual cue in ~50% of randomly selected trials. In patients with Parkinson's disease, the experiment was conducted after overnight withdrawal of antiparkinsonian drugs and again 1 h after patients had taken their usual morning medication. Patients showed improvements in the peak rate of force development and the magnitude of force developed when loud auditory stimuli accompanied visual cues. Equally, they showed improvements in the times taken to reach the peak rate of force development and their maximal force. The paradoxical facilitatory effect of sound was similar whether patients were off or on their usual antiparkinsonian medication, and could be reproduced in age-matched healthy controls. We conclude that motor improvement induced by loud auditory stimuli in Parkinson's disease is related to a physiological phenomenon which survives both with and after withdrawal of antiparkinsonian medication. The potential independence of the mediating pathways from the dopaminergic system provides impetus for further investigation as it may yield a novel nondopaminergic target for therapeutic manipulation in Parkinson's disease.
Network architectures supporting learnability.
Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 2020

Human learners acquire complex interconnected networks of relational knowledge. The capacity for such learning naturally depends on two factors: the architecture (or informational structure) of the knowledge network itself and the architecture of the computational unit-the brain-that encodes and processes the information. That is, learning is reliant on integrated network architectures at two levels: the epistemic and the computational, or the conceptual and the neural. Motivated by a wish to understand conventional human knowledge, here, we discuss emerging work assessing network constraints on the learnability of relational knowledge, and theories from statistical physics that instantiate the principles of thermodynamics and information theory to offer an explanatory model for such constraints. We then highlight similarities between those constraints on the learnability of relational networks, at one level, and the physical constraints on the development of interconnected patterns in neural systems, at another level, both leading to hierarchically modular networks. To support our discussion of these similarities, we employ an operational distinction between the modeller (e.g. the human brain), the model (e.g. a single human's knowledge) and the modelled (e.g. the information present in our experiences). We then turn to a philosophical discussion of whether and how we can extend our observations to a claim regarding explanation and mechanism for knowledge acquisition. What relation between hierarchical networks, at the conceptual and neural levels, best facilitate learning? Are the architectures of optimally learnable networks a topological reflection of the architectures of comparably developed neural networks? Finally, we contribute to a unified approach to hierarchies and levels in biological networks by proposing several epistemological norms for analysing the computational brain and social epistemes, and for developing pedagogical principles conducive to curious thought. This article is part of the theme issue 'Unifying the essential concepts of biological networks: biological insights and philosophical foundations'.
Self administration of oxycodone by adolescent and adult mice affects striatal neurotransmitter receptor gene expression.
Neuroscience, 2014

Illicit use of prescription opioid analgesics (e.g., oxycodone) in adolescence is a pressing public health issue. Our goal was to determine whether oxycodone self administration differentially affects striatal neurotransmitter receptor gene expression in the dorsal striatum of adolescent compared to adult C57BL/6J mice. Groups of adolescent mice (4 weeks old, n=12) and of adult mice (11 weeks old, n=11) underwent surgery during which a catheter was implanted into their jugular veins. After recovering from surgery, mice self administered oxycodone (0.25 mg/kg/infusion) 2 h/day for 14 consecutive days or served as yoked saline controls. Mice were sacrificed within 1h after the last self-administration session and the dorsal striatum was isolated for mRNA analysis. Gene expression was analyzed with real time PCR using a commercially available neurotransmitter receptor PCR array containing 84 genes. We found that adolescent mice self administered less oxycodone than adult mice over the 14 days. Monoamine oxidase A (Maoa) and neuropeptide Y receptor 5 mRNA levels were lower in adolescent mice than in adult mice without oxycodone exposure. Oxycodone self administration increased Maoa mRNA levels compared to controls in both age groups. There was a positive correlation of the amount of oxycodone self administered in the last session or across 14 sessions with Maoa mRNA levels. Gastrin-releasing peptide receptor mRNA showed a significant Drug × Age interaction, with point-wise significance. More genes in the dorsal striatum of adolescents (19) changed in response to oxycodone self administration compared to controls than in adult (4) mice. Overall, this study demonstrates that repeated oxycodone self administration alters neurotransmitter receptors gene expression in the dorsal striatum of adolescent and adult mice.
Effects of antenatal dexamethasone and hyperglycemia on cardiovascular adaptation to asphyxia in preterm fetal sheep.
American journal of physiology. Regulatory, integrative and comparative physiology, 2020

Antenatal glucocorticoids improve outcomes among premature infants but are associated with hyperglycemia, which can exacerbate hypoxic-ischemic injury. It is still unclear how antenatal glucocorticoids or hyperglycemia modulate fetal cardiovascular adaptations to severe asphyxia. In this study, preterm fetal sheep received either saline or 12 mg im maternal dexamethasone, followed 4 h later by complete umbilical cord occlusion (UCO) for 25 min. An additional cohort of fetuses received titrated glucose infusions followed 4 h later by UCO to control for the possibility that hyperglycemia contributed to the cardiovascular effects of dexamethasone. Fetuses were studied for 7 days after UCO. Maternal dexamethasone was associated with fetal hyperglycemia (
An interpretative phenomenological analysis of young people's self-harm in the context of interpersonal stressors and supports: Parents, peers, and clinical services.
Social science & medicine (1982), 2018

Self-harm in young people is of significant clinical concern. Multiple psychological, social and clinical factors contribute to self-harm, but it remains a poorly understood phenomenon with limited effective treatment options.
Supraspinal peroxynitrite modulates pain signaling by suppressing the endogenous opioid pathway.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012

Peroxynitrite (PN, ONOO(-)) is a potent oxidant and nitrating agent that contributes to pain through peripheral and spinal mechanisms, but its supraspinal role is unknown. We present evidence here that PN in the rostral ventromedial medulla (RVM) is essential for descending nociceptive modulation in rats during inflammatory and neuropathic pain through PN-mediated suppression of opioid signaling. Carrageenan-induced thermal hyperalgesia was associated with increased 3-nitrotyrosine (NT), a PN biomarker, in the RVM. Furthermore, intra-RVM microinjections of the PN decomposition catalyst Fe(III)-5,10,15,20-tetrakis(N-methyl-pyridinium-4-yl)porphyrin (FeTMPyP(5+)) dose-dependently reversed this thermal hyperalgesia. These effects of FeTMPyP(5+) were abrogated by intra-RVM naloxone, implicating potential interplay between PN and opioids. In support, we identified NT colocalization with the endogenous opioid enkephalin (ENK) in the RVM during thermal hyperalgesia, suggesting potential in situ interactions. To address the functional significance of such interactions, we exposed methionine-enkephalin (MENK) to PN and identified the major metabolite, 3-nitrotyrosine-methionine-sulfoxide (NSO)-MENK, using liquid chromatography-mass spectrometry. Next, we isolated, purified, and tested NSO-MENK for opioid receptor binding affinity and analgesic effects. Compared to MENK, this NSO-MENK metabolite lacked appreciable binding affinity for δ, μ, and κ opioid receptors. Intrathecal injection of NSO-MENK in rats did not evoke antinociception, suggesting that PN-mediated chemical modifications of ENK suppress opioid signaling. When extended to chronic pain, intra-RVM FeTMPyP(5+) produced naloxone-sensitive reversal of mechanical allodynia in rats following chronic constriction injury of the sciatic nerve. Collectively, our data reveal the central role of PN in RVM descending facilitation during inflammatory and neuropathic pain potentially through anti-opioid activity.