rudyvdbrink/CitationDatabase huggingface dataset:
Hypothalamic Non-AgRP, Non-POMC GABAergic Neurons Are Required for Postweaning Feeding and NPY Hyperphagia.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015

The hypothalamus is critical for feeding and body weight regulation. Prevailing studies focus on hypothalamic neurons that are defined by selectively expressing transcription factors or neuropeptides including those expressing proopiomelanocortin (POMC) and agouti-related peptides (AgRP). The Cre expression driven by the pancreas-duodenum homeobox 1 promoter is abundant in several hypothalamic nuclei but not in AgRP or POMC neurons. Using this line, we generated mice with disruption of GABA release from a major subset of non-POMC, non-AgRP GABAergic neurons in the hypothalamus. These mice exhibited a reduction in postweaning feeding and growth, and disrupted hyperphagic responses to NPY. Disruption of GABA release severely diminished GABAergic input to the paraventricular hypothalamic nucleus (PVH). Furthermore, disruption of GABA-A receptor function in the PVH also reduced postweaning feeding and blunted NPY-induced hyperphagia. Given the limited knowledge on postweaning feeding, our results are significant in identifying GABA release from a major subset of less appreciated hypothalamic neurons as a key mediator for postweaning feeding and NPY hyperphagia, and the PVH as one major downstream site that contributes significantly to the GABA action. Significance statement: Prevalent studies on feeding in the hypothalamus focus on well characterized, selective groups neurons [e.g., proopiomelanocortin (POMC) and agouti-related peptide (AgRP) neurons], and as a result, the role of the majority of other hypothalamic neurons is largely neglected. Here, we demonstrated an important role for GABAergic projections from non-POMC non-AgRP neurons to the paraventricular hypothalamic nucleus in promoting postweaning (mainly nocturnal) feeding and mediating NPY-induced hyperphagia. Thus, these results signify an importance to study those yet to be defined hypothalamic neurons in the regulation of energy balance and reveal a neural basis for postweaning (nocturnal) feeding and NPY-mediated hyperphagia.
Biasing visual selection: functional neuroimaging of the interplay between spatial cueing and feature memory guidance.
Neuropsychologia, 2011

The authors investigate the interplay between spatial attention and memory-based feature guidance of visual selection. Three types of guidance were tested: working memory, spatial cueing and passive memory. In all cases the memory-cue was not relevant to a subsequent search task, whilst the spatial cue always provided valid information. Behaviourally, search performance was influenced by spatial cueing and by feature-based cueing from the contents of working memory; both forms of guidance interacted, with feature guidance being more effective when the target's location was not pre-cued. Spatial cueing recruited the dorsal fronto-parietal network which was silent during the WM-only condition. Memory guidance of selection was reflected in activity in a frontal-temporal-occipital network. Interestingly, when spatial and memory guidance were pitted against each other, neural activity in this latter network was greatly attenuated. Connectivity analysis showed that the posterior parietal cortices inhibit the responses of occipital and temporal regions to the onset of memory-items in the search display. In the presence of a reliable spatial cue the posterior parietal cortex resumes control of attentional deployment. These results illustrate how different forms of attention guidance interact to optimise visual selection.
Hippocampus, time, and memory--a retrospective analysis.
Behavioral neuroscience, 2013

In 1984, there was considerable evidence that the hippocampus was important for spatial learning and some evidence that it was also involved in duration discrimination. The article "Hippocampus, Time, and Memory" (Meck, Church, & Olton, 1984), however, was the first to isolate the effects of hippocampal damage on specific stages of temporal processing. In this review, to celebrate the 30th anniversary of Behavioral Neuroscience, we look back on factors that contributed to the long-lasting influence of this article. The major results were that a fimbria-fornix lesion (a) interferes with the ability to retain information in temporal working memory, and (b) distorts the content of temporal reference memory, but (c) did not decrease sensitivity to signal duration. This was the first lesion experiment in which the results were interpreted by a well-developed theory of behavior (scalar timing theory). It has led to extensive research on the role of the hippocampus in temporal processing by many investigators. The most important ones are the development of computational models with plausible neural mechanisms (such as the striatal beat-frequency model of interval timing), the use of multiple behavioral measures of timing, and empirical research on the neural mechanisms of timing and temporal memory using ensemble recording of neurons in prefrontal-striatal-hippocampal circuits.
Chronic Alcohol Consumption Results in Greater Damage to the Pancreas Than to the Liver in the Rats.
The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology, 2015

Alcohol consumption increases the risk of type 2 diabetes. However, its effects on prediabetes or early diabetes have not been studied. We investigated endoplasmic reticulum (ER) stress in the pancreas and liver resulting from chronic alcohol consumption in the prediabetes and early stages of diabetes. We separated Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a type-2 diabetic animal model, into two groups based on diabetic stage: prediabetes and early diabetes were defined as occurrence between the ages of 11 to 16 weeks and 17 to 22 weeks, respectively. The experimental group received an ethanol-containing liquid diet for 6 weeks. An intraperitoneal glucose tolerance test was conducted after 16 and 22 weeks for the prediabetic and early diabetes groups, respectively. There were no significant differences in body weight between the control and ethanol groups. Fasting and 120-min glucose levels were lower and higher, respectively, in the ethanol group than in the control group. In prediabetes rats, alcohol induced significant expression of ER stress markers in the pancreas; however, alcohol did not affect the liver. In early diabetes rats, alcohol significantly increased most ER stress-marker levels in both the pancreas and liver. These results indicate that chronic alcohol consumption increased the risk of diabetes in prediabetic and early diabetic OLETF rats; the pancreas was more susceptible to damage than was the liver in the early diabetic stages, and the adaptive and proapoptotic pathway of ER stress may play key roles in the development and progression of diabetes affected by chronic alcohol ingestion.
Quantifying between-cohort and between-sex genetic heterogeneity in major depressive disorder.
American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics, 2019

Major depressive disorder (MDD) is clinically heterogeneous with prevalence rates twice as high in women as in men. There are many possible sources of heterogeneity in MDD most of which are not measured in a sufficiently comparable way across study samples. Here, we assess genetic heterogeneity based on two fundamental measures, between-cohort and between-sex heterogeneity. First, we used genome-wide association study (GWAS) summary statistics to investigate between-cohort genetic heterogeneity using the 29 research cohorts of the Psychiatric Genomics Consortium (PGC; N cases = 16,823, N controls = 25,632) and found that some of the cohort heterogeneity can be attributed to ascertainment differences (such as recruitment of cases from hospital vs. community sources). Second, we evaluated between-sex genetic heterogeneity using GWAS summary statistics from the PGC, Kaiser Permanente GERA, UK Biobank, and the Danish iPSYCH studies but did not find convincing evidence for genetic differences between the sexes. We conclude that there is no evidence that the heterogeneity between MDD data sets and between sexes reflects genetic heterogeneity. Larger sample sizes with detailed phenotypic records and genomic data remain the key to overcome heterogeneity inherent in assessment of MDD.
Colocalization of aromatase in spinal cord astrocytes: differences in expression and relationship to mechanical and thermal hyperalgesia in murine models of a painful and a non-painful bone tumor.
Neuroscience, 2015

While spinal cord astrocytes play a key role in the generation of cancer pain, there have been no studies that have examined the relationship of tumor-induced astrocyte activation and aromatase expression during the development of cancer pain. Here, we examined tumor-induced mechanical hyperalgesia and cold allodynia, and changes in Glial fibrillary acid protein (GFAP) and aromatase expression in murine models of painful and non-painful bone cancer. We demonstrate that implantation of fibrosarcoma cells, but not melanoma cells, produces robust mechanical hyperalgesia and cold allodynia in tumor-bearing mice compared to saline-injected controls. Secondly, this increase in mechanical hyperalgesia and cold allodynia is mirrored by significant increases in both spinal astrocyte activity and aromatase expression in the dorsal horn of fibrosarcoma-bearing mice. Importantly, we show that aromatase is only found within a subset of astrocytes and not in neurons in the lumbar spinal cord. Finally, administration of an aromatase inhibitor reduced tumor-induced hyperalgesia in fibrosarcoma-bearing animals. We conclude that a painful fibrosarcoma tumor induces a significant increase in spinal astrocyte activation and aromatase expression and that the up-regulation of aromatase plays a role in the development of bone tumor-induced hyperalgesia. Since spinal aromatase is also upregulated, but to a lesser extent, in non-painful melanoma bone tumors, it may also be neuroprotective and responsive to the changing tumor environment.
The P2Y2 receptor sensitizes mouse bladder sensory neurons and facilitates purinergic currents.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010

Sensitization of bladder afferents is an underlying contributor to the development and maintenance of painful bladder syndrome/interstitial cystitis. Extracellular purines and pyrimidines (e.g., ATP and UTP), released during bladder distension or from damaged cells after tissue insult, are thought to play an important role in bladder physiological and pathological states by actions at ionotropic P2X and metabotropic P2Y receptors. In the present study, we examined the ability of P2Y receptors to sensitize and modulate P2X-mediated responses in mouse bladder sensory neurons. UTP (a P2Y(2) and P2Y(4) agonist) increased excitability of bladder neurons by depolarizing resting membrane potential, increasing action potential firing, and facilitating responses to suprathreshold current injection as well as to P2X agonist application. These effects of UTP on bladder neuron excitability were blocked by the P2Y(2) receptor antagonist suramin. UTP also facilitated bladder neuron homomeric P2X(2) sustained currents and homomeric P2X(3) fast currents. The facilitatory effect of UTP on P2X(2) sustained currents was mediated by a G-protein-coupled P2Y(2) receptor/PKC pathway, whereas the effect of UTP on P2X(3) fast currents was G-protein independent. We also examined P2X and P2Y receptor expression in bladder neurons. P2Y(2) and P2Y(4) transcripts were detected in approximately 50 and approximately 20% of bladder neurons, respectively. Approximately 50% of P2X(2)- and P2X(3)-positive bladder neurons expressed P2Y(2) transcripts, whereas < or =25% of the same bladder neurons expressed P2Y(4) transcripts. These results support involvement of P2Y(2) receptors in bladder sensation, suggesting an important contribution to bladder neuron excitability and hypersensitivity.
Atypical attentional networks and the emergence of autism.
Neuroscience and biobehavioral reviews, 2013

The sociocommunicative impairments that define autism spectrum disorder (ASD) are not present at birth but emerge gradually over the first two years of life. In typical development, basic attentional processes may provide a critical foundation for sociocommunicative abilities. Therefore early attentional dysfunction in ASD may result in atypical development of social communication. Prior research has demonstrated that persons with ASD exhibit early and lifelong impairments in attention. The primary aim of this paper is to provide a review of the extant research on attention in ASD using a framework of functionally independent attentional networks as conceptualized by Posner and colleagues: the alerting, orienting and executive control networks (Posner and Petersen, 1990; Petersen and Posner, 2012). The neural substrates and typical development of each attentional network are briefly discussed, a review of the ASD attention literature is presented, and a hypothesis is proposed that links aberrant attentional mechanisms, specifically impaired disengagement of attention, with the emergence of core ASD symptoms.
Axotomy-induced cytoskeleton changes in unmyelinated mammalian central nervous system axons.
Neuroscience, 2011

Oligodendrocyte-derived myelin retards the ability of CNS axons to regenerate following transection. The intrinsic response of CNS axons to an axotomy insult may be vastly different in the absence of myelin. However, the paucity of adequate experimental models has limited detailed investigation of cellular behaviour following axon transection in an unmyelinated CNS environment. In this study we perform laser-induced axotomy of the porcine retinal ganglion cell axon, a physiologically unmyelinated, mature CNS axon that is structurally similar to humans to infer knowledge about axonal behaviour in the absence of myelin. Axotomy-induced changes to the neuronal cytoskeleton and supporting astrocytes during the early stages after transection are delineated by examining the sequence of neurofilament subunit, microtubule (TUB), microtubule associated protein (MAP), glial fibrillary acidic protein (GFAP) and terminal deoxynucleotidyl transferase biotin-dUTP nick end labelling (TUNEL) modification. Axonal transection induced an increase in the expression of neurofilament light at regions within, and immediately adjacent to, sites of axotomy. Other neurofilament subunits were not altered at sites of transection. Unlike myelinated axons where an increase in GFAP staining within hypertrophic glial scars have been shown to inhibit axonal repair we demonstrate a decrease in GFAP staining within regions of increased or preserved neurofilament expression. The behaviour of TUB and MAP proteins following transection of unmyelinated CNS axons are similar to what has previously been described in myelinated CNS axons. This study provides fundamental insights into astrocyte and axonal behaviour acutely after axotomy and demonstrates a series of degenerative events in unmyelinated CNS axons, which in comparison to prior reports are different to myelinated CNS axons. The findings of this report have relevance to understanding pathogenic mechanisms underlying neuro-degeneration in the CNS.
Activation of ADF/cofilin mediates attractive growth cone turning toward nerve growth factor and netrin-1.
Developmental neurobiology, 2010

Proper neural circuitry requires that growth cones, motile tips of extending axons, respond to molecular guidance cues expressed in the developing organism. However, it is unclear how guidance cues modify the cytoskeleton to guide growth cone pathfinding. Here, we show acute treatment with two attractive guidance cues, nerve growth factor (NGF) and netrin-1, for embryonic dorsal root ganglion and temporal retinal neurons, respectively, results in increased growth cone membrane protrusion, actin polymerization, and filamentous actin (F-actin). ADF/cofilin (AC) family proteins facilitate F-actin dynamics, and we found the inactive phosphorylated form of AC is decreased in NGF- or netrin-1-treated growth cones. Directly increasing AC activity mimics addition of NGF or netrin-1 to increase growth cone protrusion and F-actin levels. Extracellular gradients of NGF, netrin-1, and a cell-permeable AC elicit attractive growth cone turning and increased F-actin barbed ends, F-actin accumulation, and active AC in growth cone regions proximal to the gradient source. Reducing AC activity blunts turning responses to NGF and netrin. Our results suggest that gradients of NGF and netrin-1 locally activate AC to promote actin polymerization and subsequent growth cone turning toward the side containing higher AC activity.
The 2017 EULAR standardised procedures for ultrasound imaging in rheumatology.
Annals of the rheumatic diseases, 2017

In 2001, the European League Against Rheumatism developed and disseminated the first guidelines for musculoskeletal (MS) ultrasound (US) in rheumatology. Fifteen years later, the dramatic expansion of new data on MSUS in the literature coupled with technological developments in US imaging has necessitated an update of these guidelines.
Activity-driven relaxation of the cortical actomyosin II network synchronizes Munc18-1-dependent neurosecretory vesicle docking.
Nature communications, 2015

In neurosecretory cells, secretory vesicles (SVs) undergo Ca(2+)-dependent fusion with the plasma membrane to release neurotransmitters. How SVs cross the dense mesh of the cortical actin network to reach the plasma membrane remains unclear. Here we reveal that, in bovine chromaffin cells, SVs embedded in the cortical actin network undergo a highly synchronized transition towards the plasma membrane and Munc18-1-dependent docking in response to secretagogues. This movement coincides with a translocation of the cortical actin network in the same direction. Both effects are abolished by the knockdown or the pharmacological inhibition of myosin II, suggesting changes in actomyosin-generated forces across the cell cortex. Indeed, we report a reduction in cortical actin network tension elicited on secretagogue stimulation that is sensitive to myosin II inhibition. We reveal that the cortical actin network acts as a 'casting net' that undergoes activity-dependent relaxation, thereby driving tethered SVs towards the plasma membrane where they undergo Munc18-1-dependent docking.
Distinct effects of early-life experience and trait aggression on cardiovascular reactivity and recovery.
Physiology & behavior, 2019

We previously demonstrated independent effects of early-life experience (ELE) and trait aggression (TA) on resting heart rate (HR) and mean arterial pressure (MAP) in rats. The present study examined the effects of TA and ELE on stress-evoked cardiovascular reactivity and recovery. Pups born to Wistar-Kyoto dams were exposed to daily 180-min periods of maternal separation (MS) during the first two weeks of life, and aggression was assessed in adult offspring using the resident-intruder test. Radiotelemetry was then used to record stress-evoked HR and MAP responses in response to: strobe light, novel environment, intruder rat, or restraint. Maximal HR and MAP responses were quantified as indices of reactivity, and exponential decay curves were fitted to determine decay constants as a measure of recovery. Strobe light was the weakest stressor, evoking the lowest increases in MAP and HR, which were significantly greater in MS-exposed rats irrespective of TA. In contrast, reactivity to and recovery from exposure to a novel environment or an intruder were significantly influenced by TA, but not ELE. TA animals exhibited greater reactivity in both of these paradigms, with either decreased (novel environment) or increased (intruder) recovery. Restraint stress induced the largest changes in HR and MAP with the slowest recovery, and these responses were shaped by a significant ELE x TA interaction. These data indicate that cardiovascular reactivity and recovery are influenced by ELE, TA, or ELE x TA interaction depending on stressor aversiveness as well as its physical and psychological dimensions.
Cardiac sympathectomy and spinal cord stimulation attenuate reflex-mediated norepinephrine release during ischemia preventing ventricular fibrillation.
JCI insight, 2019

The purpose of this study was to define the mechanism by which cardiac neuraxial decentralization or spinal cord stimulation (SCS) reduces ischemia-induced ventricular fibrillation (VF). Direct measurements of norepinephrine (NE) levels in the left ventricular interstitial fluid (ISF) by microdialysis, in response to transient (15-minute) coronary artery occlusion (CAO), were performed in anesthetized canines. Responses were studied in animals with intact neuraxes and were compared with those in which the intrathoracic component of the cardiac neuraxes (stellate ganglia) or the intrinsic cardiac neuronal (ICN) system was surgically delinked from the central nervous system and those with intact neuraxes with preemptive SCS (T1-T3). With intact neuraxes, animals with exaggerated NE release due to CAO were at increased risk for VF. During CAO, there was a 152% increase in NE when the neuraxes were intact compared with 114% following stellate decentralization and 16% following ICN decentralization. During SCS, CAO NE levels increased by 59%. Risk for CAO-induced VF was 38% in controls, 8% following decentralization, and 11% following SCS. These data indicate that ischemia-related afferent neuronal transmission differentially engages central and intrathoracic sympathetic reflexes and amplifies sympathoexcitation. Differences in regional ventricular NE release are associated with increased risk for VF. Surgical decentralization or SCS reduced NE release and VF.
Evaluation of the For Our Children's Sake intervention, parental support in prison to influence positive parenting: study protocol for a controlled trial.
BMJ open, 2020

Children of incarcerated parents comprise a greatly disadvantaged group in society and positive parenting constitutes an important factor for children's healthy development. Internationally developed parenting interventions for incarcerated parents suggest an impact on parenting outcomes, but no such evaluation has been undertaken in Sweden.This study aims to investigate the effects of the parenting programme currently offered in prisons in Sweden, For Our Children's Sake (FOCS), through a controlled trial with a parallel implementation process evaluation.