rudyvdbrink/CitationDatabase huggingface dataset:
Perchlorate exposure does not modulate temporal variation of whole-body thyroid and androgen hormone content in threespine stickleback.
General and comparative endocrinology, 2015

Previously we showed that exposure of threespine stickleback (Gasterosteus aculeatus) to the endocrine disruptor perchlorate results in pronounced structural changes in thyroid and gonad, while surprisingly, whole-body thyroid hormone concentrations remain unaffected. To test for hormone titer variations on a finer scale, we evaluated the interactive effects of time (diel and reproductive season) and perchlorate exposure on whole-body contents of triiodothyronine (T3), thyroxine (T4), and 11-ketotestosterone (11-KT) in captive stickleback. Adult stickleback were exposed to 100ppm perchlorate or control water and sampled at 4-h intervals across the 24-hday and at one time-point (1100h) weekly across the reproductive season (May-July). Neither whole-body T3 nor T4 concentration significantly differed across the day in control or perchlorate treated stickleback. Across the reproductive season, whole-body T3 concentration remained stable while T4 significantly increased. However, neither hormone concentration was significantly affected by perchlorate, verifying our previous studies. The concentration of whole-body 11-KT, a major fish androgen, displayed significant diel variation and also steadily declined across the reproductive season in untreated males; perchlorate exposure did not influence the concentration of 11-KT in either diel or reproductive season schedules. Diel and reproductive season variations in 11-KT content in male stickleback are likely related to reproductive physiology and behavior. The observed increase in T4 content across the reproductive season may be reflective of increased energy investment in reproduction near the end of the life cycle.
Role of synucleins in Alzheimer's disease.
Neurotoxicity research, 2009

Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common causes of dementia and movement disorders in the elderly. While progressive accumulation of oligomeric amyloid-beta protein (Abeta) has been identified as one of the central toxic events in AD leading to synaptic dysfunction, accumulation of alpha-synuclein (alpha-syn) resulting in the formation of oligomers has been linked to PD. Most of the studies in AD have been focused on investigating the role of Abeta and Tau; however, recent studies suggest that alpha-syn might also play a role in the pathogenesis of AD. For example, fragments of alpha-syn can associate with amyloid plaques and Abeta promotes the aggregation of alpha-syn in vivo and worsens the deficits in alpha-syn tg mice. Moreover, alpha-syn has also been shown to accumulate in limbic regions in AD, Down's syndrome, and familial AD cases. Abeta and alpha-syn might directly interact under pathological conditions leading to the formation of toxic oligomers and nanopores that increase intracellular calcium. The interactions between Abeta and alpha-syn might also result in oxidative stress, lysosomal leakage, and mitochondrial dysfunction. Thus, better understanding the steps involved in the process of Abeta and alpha-syn aggregation is important in order to develop intervention strategies that might prevent or reverse the accumulation of toxic proteins in AD.
Dysfunction in endoplasmic reticulum-mitochondria crosstalk underlies SIGMAR1 loss of function mediated motor neuron degeneration.
Brain : a journal of neurology, 2015

Mutations in Sigma 1 receptor (SIGMAR1) have been previously identified in patients with amyotrophic lateral sclerosis and disruption of Sigmar1 in mouse leads to locomotor deficits. However, cellular mechanisms underlying motor phenotypes in human and mouse with disturbed SIGMAR1 function have not been described so far. Here we used a combination of in vivo and in vitro approaches to investigate the role of SIGMAR1 in motor neuron biology. Characterization of Sigmar1(-/-) mice revealed that affected animals display locomotor deficits associated with muscle weakness, axonal degeneration and motor neuron loss. Using primary motor neuron cultures, we observed that pharmacological or genetic inactivation of SIGMAR1 led to motor neuron axonal degeneration followed by cell death. Disruption of SIGMAR1 function in motor neurons disturbed endoplasmic reticulum-mitochondria contacts, affected intracellular calcium signalling and was accompanied by activation of endoplasmic reticulum stress and defects in mitochondrial dynamics and transport. These defects were not observed in cultured sensory neurons, highlighting the exacerbated sensitivity of motor neurons to SIGMAR1 function. Interestingly, the inhibition of mitochondrial fission was sufficient to induce mitochondria axonal transport defects as well as axonal degeneration similar to the changes observed after SIGMAR1 inactivation or loss. Intracellular calcium scavenging and endoplasmic reticulum stress inhibition were able to restore mitochondrial function and consequently prevent motor neuron degeneration. These results uncover the cellular mechanisms underlying motor neuron degeneration mediated by loss of SIGMAR1 function and provide therapeutically relevant insight into motor neuronal diseases.
Strain differences in response to traumatic brain injury in Long-Evans compared to Sprague-Dawley rats.
Journal of neurotrauma, 2009

The selected strain of rodent used in experimental models of traumatic brain injury is typically dependent upon the experimental questions asked and the familiarity of the investigator with a specific rodent strain. This archival study compares the injury responsiveness and recovery profiles of two popular outbred strains, the Long-Evans (LE) and the Sprague-Dawley (SD), after brain injury induced by lateral fluid percussion injury (LFPI). General findings include a significantly longer duration of unconsciousness in LE rats, but similar durations of apnea. Both strains displayed the same level of initial FPI-induced behavioral deficits, followed by a more rapid rate of functional recovery in SD rats. Cortical volume loss was not significantly different, but close inspection of the data suggests the possibility that LE rats may be more susceptible to damage in the hemisphere contralateral to the injury site than are SD rats. It is hoped that the information provided here encourages greater attention to the subtle differences and similarities between strains in future pre-clinical efficacy studies of traumatic brain injury.
Neural correlates of dysfunctional emotion regulation in major depressive disorder. A systematic review of neuroimaging studies.
Neuroscience and biobehavioral reviews, 2013

Abnormal emotion processing is a core feature of major depressive disorder (MDD). Since the emergence of functional neuroimaging techniques, many studies have been conducted in MDD subjects to elucidate the underlying abnormalities in the neural systems involved in emotion regulation. In this systematic review, we discuss this research in the context of the neural model of emotion regulation previously described by Phillips et al. (2008). This model differentiates between automatic and voluntary emotion regulation subprocesses. Automatic regulation subprocesses were shown to involve predominantly medial prefrontal cortical structures, in addition to the hippocampus and parahippocampus, while voluntary regulation processes additionally recruited lateral prefrontal cortical regions. In conclusion, although the available data is limited, findings suggest that MDD subjects demonstrate abnormally reduced activity in lateral prefrontal cortices during explicit voluntary control of emotional experience. During early, automatic stages of emotion regulation, on the other hand, MDD subjects appear to achieve successful emotion regulation by recruiting additional lateral prefrontal neural regions, that may be mediated by medial prefrontal, especially rostral/dorsal anterior cingulate gyrus (ACG) functioning. Dysfunctional automatic regulation may impair successful voluntary emotion regulation, and may present a target for novel therapeutic approaches in MDD.
Peripherally derived macrophages modulate microglial function to reduce inflammation after CNS injury.
PLoS biology, 2018

Infiltrating monocyte-derived macrophages (MDMs) and resident microglia dominate central nervous system (CNS) injury sites. Differential roles for these cell populations after injury are beginning to be uncovered. Here, we show evidence that MDMs and microglia directly communicate with one another and differentially modulate each other's functions. Importantly, microglia-mediated phagocytosis and inflammation are suppressed by infiltrating macrophages. In the context of spinal cord injury (SCI), preventing such communication increases microglial activation and worsens functional recovery. We suggest that macrophages entering the CNS provide a regulatory mechanism that controls acute and long-term microglia-mediated inflammation, which may drive damage in a variety of CNS conditions.
Transcranial magnetic stimulation of the primary motor cortex modulates response interference in a flanker task.
Neuroscience letters, 2009

In a typical flanker task, responses to a central target ("S" or "N") are modulated by whether the flankers are compatible ("SSSSS") or incompatible ("NNSNN"), with increased reaction times and decreased accuracy on incompatible trials. The role of the motor system in response interference under these conditions remains unclear, however. Here we show that transcranial magnetic stimulation (TMS) of the left primary motor cortex modulates the amount of flanker interference depending on the hand used for the response. Left motor TMS delivered at 200ms after the onset of the array increased interference from incompatible flankers ("SSNSS") when the target response was associated with the contralateral motor response (i.e. for "N" responses with the right hand), relative to when responses were to targets using the (left) hand ipsilateral to the site of TMS. Interestingly, under identical conditions, the degree of flanker interference was reduced when the TMS pulse was applied later in time. The analyses of the TMS-induced motor evoked potentials pointed to motor activity varying in the same conditions. We discuss the implications for understanding response interference and the role of the primary motor cortex in response selection.
Cortical inhibition of laser pain and laser-evoked potentials by non-nociceptive somatosensory input.
The European journal of neuroscience, 2015

Although the inhibitory action that tactile stimuli can have on pain is well documented, the precise timing of the interaction between the painful and non-painful stimuli in the central nervous system is unclear. The aim of this study was to investigate this issue by measuring the timing of the amplitude modulation of laser evoked potentials (LEPs) due to conditioning non-painful stimuli. LEPs were recorded from 31 scalp electrodes in 10 healthy subjects after painful stimulation of the right arm (C6-C7 dermatomes). Non-painful electrical stimuli were applied by ring electrodes on the second and third finger of the right hand. Electrical stimuli were delivered at +50, +150, +200 and +250 ms interstimulus intervals (ISIs) after the laser pulses. LEPs obtained without any conditioning stimulation were used as a baseline. As compared to the baseline, non-painful electrical stimulation reduced the amplitude of the vertex N2/P2 LEP component and the laser pain rating when electrical stimuli followed the laser pulses only at +150 and +200 ms ISIs. As at these ISIs the collision between the non-painful and painful input is likely to take place at the cortical level, we can conclude that the late processing of painful (thermal) stimuli is partially inhibited by the processing of non-painful (cutaneous) stimuli within the cerebral cortex. Moreover, our results do not provide evidence that non-painful inputs can inhibit pain at a lower level, including the spinal cord.
Pornography Use and Sexual Health among Same-Sex and Mixed-Sex Couples: An Event-Level Dyadic Analysis.
Archives of sexual behavior, 2021

A large number of partnered individuals regularly use or are in a relationship with someone who uses pornography. However, knowledge concerning the association between pornography use and partnered sexual health-sexual satisfaction, distress, and function-is fragmentary. The current study used an event-level dyadic design to examine the associations between pornography use and sexual satisfaction, distress, and function on days when partnered sexual activity occurred. A convenience sample of 217 couples (M
Action-Based Learning of Multistate Objects in the Medial Temporal Lobe.
Cerebral cortex (New York, N.Y. : 1991), 2016

Actions constrain perception by changing the appearance of objects in the environment. As such, they provide an interactive basis for learning the structure of visual input. If an action systematically transforms one stimulus into another, then these stimuli are more likely to reflect different states of the same persisting object over time. Here we show that such multistate objects are represented in the human medial temporal lobe--the result of a mechanism in which actions influence associative learning of how objects transition between states. We further demonstrate that greater recruitment of these action-based representations during object perception is accompanied by attenuated activity in stimulus-selective visual cortex. In this way, our interactions with the environment help build visual knowledge that predictively facilitates perceptual processing.
'Where' and 'what' in the whisker sensorimotor system.
Nature reviews. Neuroscience, 2008

In the visual system of primates, different neuronal pathways are specialized for processing information about the spatial coordinates of objects and their identity - that is, 'where' and 'what'. By contrast, rats and other nocturnal animals build up a neuronal representation of 'where' and 'what' by seeking out and palpating objects with their whiskers. We present recent evidence about how the brain constructs a representation of the surrounding world through whisker-mediated sense of touch. While considerable knowledge exists about the representation of the physical properties of stimuli - like texture, shape and position - we know little about how the brain represents their meaning. Future research may elucidate this and show how the transformation of one representation to another is achieved.
Adipocytokines levels at delivery, functional variation of TFAP2β, and maternal and neonatal anthropometric parameters.
Obesity (Silver Spring, Md.), 2013

Adipocytokines participate in the regulation of glucose metabolism and fetal development. The transcription factor activating protein 2B (TFAP2β) has been associated with adipocytokine regulation, and gene variations with type 2 diabetes and obesity. This study investigated associations between maternal TFAP2B variation, adipocytokine levels, and maternal and neonatal anthropometric characteristics.
Keeping in touch with one's self: multisensory mechanisms of self-consciousness.
PloS one, 2009

The spatial unity between self and body can be disrupted by employing conflicting visual-somatosensory bodily input, thereby bringing neurological observations on bodily self-consciousness under scientific scrutiny. Here we designed a novel paradigm linking the study of bodily self-consciousness to the spatial representation of visuo-tactile stimuli by measuring crossmodal congruency effects (CCEs) for the full body.
Selective mitochondrial depletion, apoptosis resistance, and increased mitophagy in human Charcot-Marie-Tooth 2A motor neurons.
Human molecular genetics, 2016

Charcot-Marie-Tooth 2A (CMT2A) is an inherited peripheral neuropathy caused by mutations in MFN2, which encodes a mitochondrial membrane protein involved in mitochondrial network homeostasis. Because MFN2 is expressed ubiquitously, the reason for selective motor neuron (MN) involvement in CMT2A is unclear. To address this question, we generated MNs from induced pluripotent stem cells (iPSCs) obtained from the patients with CMT2A as an in vitro disease model. CMT2A iPSC-derived MNs (CMT2A-MNs) exhibited a global reduction in mitochondrial content and altered mitochondrial positioning without significant differences in survival and axon elongation. RNA sequencing profiles and protein studies of key components of the apoptotic executioner program (i.e. p53, BAX, caspase 8, cleaved caspase 3, and the anti-apoptotic marker Bcl2) demonstrated that CMT2A-MNs are more resistant to apoptosis than wild-type MNs. Exploring the balance between mitochondrial biogenesis and the regulation of autophagy-lysosome transcription, we observed an increased autophagic flux in CMT2A-MNs that was associated with increased expression of PINK1, PARK2, BNIP3, and a splice variant of BECN1 that was recently demonstrated to be a trigger for mitochondrial autophagic removal. Taken together, these data suggest that the striking reduction in mitochondria in MNs expressing mutant MFN2 is not the result of impaired biogenesis, but more likely the consequence of enhanced mitophagy. Thus, these pathways represent possible novel molecular therapeutic targets for the development of an effective cure for this disease.
Ventral mesencephalon astrocytes are more efficient than those of other regions in inducing dopaminergic neurons through higher expression level of TGF-beta3.
Journal of molecular neuroscience : MN, 2009

Being supportive cells for neurons in the central nervous system, astrocytes have recently found to be associated with neurogenesis. Ventral mesencephalon (VM) astrocytes were also detected being instructive for VM dopaminergic (DA) neurogenesis, but the underling mechanisms are still unclear. This research is to figure out whether VM astrocytes are more efficient than those from other brain regions in inducing VM DA neurons from their precursors and whether transforming growth factor-betas (TGF-betas) are the underlying molecules. We found that, compared with astrocytes preparations from striatum and hippocampus, VM astrocytes preparations displayed markedly higher efficacy in inducing DA neurogenesis. Besides, they also expressed higher level of TGF-beta3 than those of two other regions. When TGF-beta3 gene expression in astrocytes preparations was inhibited by its antisense oligonucleotide, the induction of DA neurons decreased to a similar level among these three astrocytes preparations. Thus, our experiment indicates that VM astrocytes preparations which contained highly purified astrocytes are more efficient in inducing DA neurogenesis than those from other regions. Furthermore, it also suggests that the regional differences are regulated by different expression levels of TGF-beta3 in those astrocytes preparations from different derivations.
Inhibition of T-type calcium channels and hydrogen sulfide-forming enzyme reverses paclitaxel-evoked neuropathic hyperalgesia in rats.
Neuroscience, 2011

Hydrogen sulfide (H₂S), a gasotransmitter, facilitates pain sensation by targeting Ca(v)3.2 T-type calcium channels. The H₂S/Ca(v)3.2 pathway appears to play a role in the maintenance of surgically evoked neuropathic pain. Given evidence that chemotherapy-induced neuropathic pain is blocked by ethosuximide, known to block T-type calcium channels, we examined if more selective T-type calcium channel blockers and also inhibitors of cystathionine-γ-lyase (CSE), a major H₂S-forming enzyme in the peripheral tissue, are capable of reversing the neuropathic pain evoked by paclitaxel, an anti-cancer drug. It was first demonstrated that T-type calcium channel blockers, NNC 55-0396, known to inhibit Ca(v)3.1, and mibefradil inhibited T-type currents in Ca(v)3.2-transfected HEK293 cells. Repeated systemic administration of paclitaxel caused delayed development of mechanical hyperalgesia, which was reversed by single intraplantar administration of NNC 55-0396 or mibefradil, and by silencing of Ca(v)3.2 by antisense oligodeoxynucleotides. Systemic administration of dl-propargylglycine and β-cyanoalanine, irreversible and reversible inhibitors of CSE, respectively, also abolished the established neuropathic hyperalgesia. In the paclitaxel-treated rats, upregulation of Ca(v)3.2 and CSE at protein levels was not detected in the dorsal root ganglia (DRG), spinal cord or peripheral tissues including the hindpaws, whereas H(2)S content in hindpaw tissues was significantly elevated. Together, our study demonstrates the effectiveness of NNC 55-0396 in inhibiting Ca(v)3.2, and then suggests that paclitaxel-evoked neuropathic pain might involve the enhanced activity of T-type calcium channels and/or CSE in rats, but not upregulation of Ca(v)3.2 and CSE at protein levels, differing from the previous evidence for the neuropathic pain model induced by spinal nerve cutting in which Ca(v)3.2 was dramatically upregulated in DRG.
Pure tones modulate the representation of orientation and direction in the primary visual cortex.
Journal of neurophysiology, 2019

Multimodal sensory integration facilitates the generation of a unified and coherent perception of the environment. It is now well established that unimodal sensory perceptions, such as vision, are improved in multisensory contexts. Whereas multimodal integration is primarily performed by dedicated multisensory brain regions such as the association cortices or the superior colliculus, recent studies have shown that multisensory interactions also occur in primary sensory cortices. In particular, sounds were shown to modulate the responses of neurons located in layers 2/3 (L2/3) of the mouse primary visual cortex (V1). Yet, the net effect of sound modulation at the V1 population level remained unclear. In the present study, we performed two-photon calcium imaging in awake mice to compare the representation of the orientation and the direction of drifting gratings by V1 L2/3 neurons in unimodal (visual only) or multimodal (audiovisual) conditions. We found that sound modulation depended on the tuning properties (orientation and direction selectivity) and response amplitudes of V1 L2/3 neurons. Sounds potentiated the responses of neurons that were highly tuned to the cue's orientation and direction but weakly active in the unimodal context, following the principle of inverse effectiveness of multimodal integration. Moreover, sound suppressed the responses of neurons untuned for the orientation and/or the direction of the visual cue. Altogether, sound modulation improved the representation of the orientation and direction of the visual stimulus in V1 L2/3. Namely, visual stimuli presented with auditory stimuli recruited a neuronal population better tuned to the visual stimulus orientation and direction than when presented alone.