rudyvdbrink/CitationDatabase huggingface dataset:
Toll-like receptor-induced inflammatory cytokines are suppressed by gain of function or overexpression of Gα(i2) protein.
Inflammation, 2012

Previous studies have implicated a role of Gα(i) proteins as co-regulators of Toll-like receptor (TLR) activation. These studies largely derived from examining the effect of Gα(i) protein inhibitors or genetic deletion of Gα(i) proteins. However, the effect of increased Gα(i) protein function or Gα(i) protein expression on TLR activation has not been investigated. We hypothesized that gain of function or increased expression of Gα(i) proteins suppresses TLR2- and TLR4-induced inflammatory cytokines. Novel transgenic mice with genomic "knock-in" of a regulator of G protein signaling (RGS)-insensitive Gnai2 allele (Gα(i2)(G184S/G184S) ; GS/GS) were employed. These mice express essentially normal levels of Gα(i2) protein; however, the Gα(i2) is insensitive to its negative regulator RGS thus rendering more sustained Gα(i2) protein activation following ligand/receptor binding. In subsequent studies, we generated Raw 264.7 cells that stably overexpress Gα(i2) protein (Raw Gα(i2)). Peritoneal macrophages, splenocytes, and mouse embryonic fibroblasts (MEF) were isolated from WT and GS/GS mice and were stimulated with LPS, Pam3CSK4, or Poly (I:C). We also subjected WT and GS/GS mice to endotoxic shock (LPS, 25 mg/kg i.p.) and plasma tumor necrosis factor alpha (TNF-α) and interleukin (IL)-6 production were determined. We found that in vitro LPS and Pam3CSK4-induced TNF-α, and IL-6 production are decreased in macrophages from GS/GS mice compared with WT mice (p < 0.05). In vitro, LPS and Pam3CSK4 induced IL-6 production in splenocytes, and in vivo, LPS-induced IL-6 were suppressed in GS/GS mice. Poly (I:C)-induced TNF-α, and IL-6 in vitro demonstrated no difference between GS/GS mice and WT mice. LPS-induced IL-6 production was inhibited in MEFs from GS/GS mice similarly to macrophage and splenocytes. In parallel studies, Raw Gα(i2) cells also exhibit decreased TNF-α and IL-6 production in response to LPS and Pam3CSK4. These studies support our hypothesis that Gα(i2) proteins are novel negative regulators of TLR activation.
Impact of childhood adversity on corticolimbic volumes in youth at clinical high-risk for psychosis.
Schizophrenia research, 2019

Childhood adversity is among the strongest risk factors for psychosis-spectrum disorders, though the nature and specificity of the biological mechanisms underlying this association remains unclear. Previous research reveals overlaps in the volumetric alterations observed in both adversity-exposed individuals and in psychosis-spectrum populations, highlighting the possibility that deviations in corticolimbic gray matter development may be one mechanism linking adversity and psychosis. Given that childhood adversity encompasses a wide range of adverse experiences, there is also a critical need to examine whether these different types of experiences have unique effects on corticolimbic regions. This study examined the association between childhood adversity and cortical, hippocampal, and amygdalar volume in a large sample of youth at clinical-high risk (CHR) for psychosis. We utilized a novel differentiated adversity approach that distinguishes exposures along dimensions of threat (e.g., abuse) and deprivation (e.g., poverty, neglect) to test for differential associations. Participants were drawn from the North American Prodromal Longitudinal Study (NAPLS) and completed an MRI scan and a retrospective assessment of childhood adversity at baseline. We found that deprivation exposure, but not threat, was uniquely associated with smaller cortical volume and smaller right hippocampal volume in CHR youth. These associations were masked in a generalized risk model that utilized a total adversity score. The findings suggest that deprivation exposures during childhood contribute to the subtle volumetric reductions observed in clinical high-risk samples and highlight the importance of disentangling different dimensions of adversity.
CSF biomarkers of Alzheimer's disease concord with amyloid-β PET and predict clinical progression: A study of fully automated immunoassays in BioFINDER and ADNI cohorts.
Alzheimer's & dementia : the journal of the Alzheimer's Association, 2018

We studied whether fully automated Elecsys cerebrospinal fluid (CSF) immunoassay results were concordant with positron emission tomography (PET) and predicted clinical progression, even with cutoffs established in an independent cohort.
Neurofilaments as biomarkers in neurological disorders.
Nature reviews. Neurology, 2018

Neuroaxonal damage is the pathological substrate of permanent disability in various neurological disorders. Reliable quantification and longitudinal follow-up of such damage are important for assessing disease activity, monitoring treatment responses, facilitating treatment development and determining prognosis. The neurofilament proteins have promise in this context because their levels rise upon neuroaxonal damage not only in the cerebrospinal fluid (CSF) but also in blood, and they indicate neuroaxonal injury independent of causal pathways. First-generation (immunoblot) and second-generation (enzyme-linked immunosorbent assay) neurofilament assays had limited sensitivity. Third-generation (electrochemiluminescence) and particularly fourth-generation (single-molecule array) assays enable the reliable measurement of neurofilaments throughout the range of concentrations found in blood samples. This technological advancement has paved the way to investigate neurofilaments in a range of neurological disorders. Here, we review what is known about the structure and function of neurofilaments, discuss analytical aspects and knowledge of age-dependent normal ranges of neurofilaments and provide a comprehensive overview of studies on neurofilament light chain as a marker of axonal injury in different neurological disorders, including multiple sclerosis, neurodegenerative dementia, stroke, traumatic brain injury, amyotrophic lateral sclerosis and Parkinson disease. We also consider work needed to explore the value of this axonal damage marker in managing neurological diseases in daily practice.
Automatic detection of high frequency oscillations during epilepsy surgery predicts seizure outcome.
Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology, 2016

High frequency oscillations (HFOs) and in particular fast ripples (FRs) in the post-resection electrocorticogram (ECoG) have recently been shown to be highly specific predictors of outcome of epilepsy surgery. FR visual marking is time consuming and prone to observer bias. We validate here a fully automatic HFO detector against seizure outcome.
The dynamic serotonin system of the maternal brain.
Archives of women's mental health, 2019

Many pregnant and postpartum women worldwide suffer from high anxiety and/or depression, which can have detrimental effects on maternal and infant well-being. The first-line pharmacotherapies for prepartum and postpartum affective disorders continue to be the selective serotonin reuptake inhibitors (SSRIs), despite the lack of large well-controlled studies demonstrating their efficacy in reproducing women and the potential for fetal/neonatal exposure to the drugs. Prepartum or postpartum use of SSRIs or other drugs that modulate the brain's serotonin system is also troubling because very little is known about the typical, let alone the atypical, changes that occur in the female central serotonin system across reproduction. We do know from a handful of studies of women and female laboratory rodents that numerous aspects of the central serotonin system are naturally dynamic across reproduction and are also affected by pregnancy stress (a major predisposing factor for maternal psychopathology). Thus, it should not be assumed that the maternal central serotonin system being targeted by SSRIs is identical to non-parous females or males. More information about the normative and stress-derailed changes in the maternal central serotonin system is essential for understanding how serotonin is involved in the etiology of, and the best use of SSRIs for potentially treating, affective disorders in the pregnant and postpartum populations.
Low sociability in BTBR T+tf/J mice is independent of partner strain.
Physiology & behavior, 2012

Inbred mouse strains differ greatly in social behaviors, making them a valuable resource to study genetic and non-genetic mechanisms underlying social deficits relevant to autism spectrum disorders. A hallmark symptom of autism is a lack of ability to understand other people's thoughts and intentions, which leads to impairments in adjusting behaviors in response to ever-changing social situations in daily life. We compared the ability of BTBR T+tf/J (BTBR), a strain with low sociability, and C57BL/6J (B6), a strain with high sociability, for their abilities to modulate responses to social cues from different partners in the reciprocal social interaction test. Results indicate that BTBR exhibited low sociability toward different partners and displayed minimal ability to modify behaviors toward different partners. In contrast, B6 showed high sociability toward different partners and was able to modify social behaviors toward different partners. Consistent results were found in two independent cohorts of different ages, and in both sexes. In the three-chambered test, high sociability in B6 and low sociability in BTBR were independent of strain of the novel mouse. Since social deficits in BTBR could potentially be caused by physical disabilities in detecting social olfactory cues, or in cognitive abilities, we tested BTBR and B6 mice on measures of olfaction and cognition. BTBR mice displayed more sniffing of social odors emitted by soiled bedding than of an odorless novel object, but failed to show a preference for a live novel mouse over a novel object. On olfactory habituation/dishabituation to a sequence of odors, BTBR displayed discrimination abilities across three non-social and two social odors. However, as compared to B6, BTBR displayed less sniff time for both non-social and social odors, and no significant dishabituation between cage odors from two different novel mouse strains, findings that will be important to investigate further. BTBR was generally normal in spatial acquisition on the Morris water maze test, but showed deficits in reversal learning. Time spent freezing on contextual and cued fear conditioning was lower in BTBR than in B6. Our findings suggest that BTBR has poor abilities to modulate its responses to different social partners, which may be analogous to social cognition deficits in autism, adding to the value of this strain as a mouse model of autism.
The selectivity of task-dependent attention varies with surrounding context.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012

Attention is thought to operate by enhancing the target of interest and suppressing the surroundings. We hypothesized that the spatial profile of attention depends on the surround's relationship to the target. Using high-density electroencephalographic measurements, we examined the spatial profile of attention to a grating target surrounded by an annular grating that was either coextensive with the target (unsegmented) or appeared segmented from it due to a gap or phase offset. We directly probed the spread of attention from the central target into the surround by flickering the surround and monitoring frequency-tagged steady-state visual-evoked potentials. Observers were required to detect a contrast increment that occurred only on the target. Successful detection of the increment required selecting the target and suppressing the surround, particularly when the target did not readily segment from the surround. The profile of attention was investigated in five visual regions of interest (ROIs) (V1, V4, V3A, lateral occipital complex, and human middle temporal area), mapped in a separate anatomical magnetic resonance imaging scan. We found that in most ROIs, attention to the target generated smaller responses from the surrounding annulus when it was contiguous compared with when it was clearly segmented. This result shows that the profile of attention depends on task demands and on surrounding context; attention is tightly focused when the target region needs to be isolated but loosely focused when the target region is clearly segmented.
Ischaemic stroke in young adults: a global perspective.
Journal of neurology, neurosurgery, and psychiatry, 2020

Ischaemic stroke at young age is an increasing problem in both developing and developed countries due to rising incidence, high morbidity and mortality and long-term psychological, physical and social consequences. Compared with stroke in older adults, stroke in young adults is more heterogeneous due to the wide variety of possible underlying risk factors and aetiologies. In this review, we will provide an overview of the global variation in the epidemiology of stroke in young adults, with special attention to differences in geography, ethnicity/race and sex, as well as traditional and novel risk factors for early-onset ischaemic stroke, such as air pollution. Understanding global differences is an important prerequisite for better region-specific prevention and treatment of this devastating condition.
Integration of CO2 and odorant signals in the mouse olfactory bulb.
Neuroscience, 2010

Carbon dioxide (CO(2)) is an important environmental cue for many animal species. In both vertebrates and invertebrates, CO(2) is detected by a specialized subset of olfactory sensory neurons (OSNs) and mediates several stereotypical behaviors. It remains unknown how CO(2) cues are integrated with other olfactory signals in the mammalian olfactory bulb, the first stage of central olfactory processing. By recording from the mouse olfactory bulb in vivo, we found that CO(2)-activating neurons also respond selectively to odorants, many of which are putative mouse pheromones and natural odorants. In addition, many odorant-responsive bulbar neurons are inhibited by CO(2). For a substantial number of CO(2)-activating neurons, binary mixtures of CO(2) and a specific odorant produce responses that are distinct from those evoked by either CO(2) or the odorant alone. In addition, for a substantial number of CO(2)-inhibiting neurons, CO(2) addition can completely block the action potential firing of the cells to the odorants. These results indicate strong interaction between CO(2) signals and odorant signals in the olfactory bulb, suggesting important roles for the integration of these two signals in CO(2)-mediated behavioral responses.
Genetic Inhibition of Receptor Interacting Protein Kinase-1 Reduces Cell Death and Improves Functional Outcome After Intracerebral Hemorrhage in Mice.
Stroke, 2017

Recent studies using cultured cells and rodent intracerebral hemorrhage (ICH) models have implicated RIPK1 (receptor interacting protein kinase-1) as a driver of programmed necrosis and secondary injury based on use of chemical inhibitors. However, these inhibitors have off-target effects and cannot be used alone to prove a role for RIPK1. The aim of the current study was to examine the effect of genetic inhibition of the kinase domain of RIPK1 in a mouse ICH model.
d-Cycloserine reverses scopolamine-induced object and place memory deficits in a spontaneous recognition paradigm in rats.
Pharmacology, biochemistry, and behavior, 2019

d-Cycloserine (DCS) is a partial agonist of the glutamatergic N-methyl-d-aspartate (NMDA) receptor-associated glycine site, and it prevents the amnesic effects of the muscarinic receptor antagonist scopolamine in various memory tests in rodents. In the present study, we tested the hypothesis that DCS has anti-amnesic effects in scopolamine-induced deficits using spontaneous object recognition and place recognition tests. In both tests, scopolamine (0.5 mg/kg, i.p.) was systemically administered 60 min prior to testing, while DCS (7.5, 15, 30 mg/kg, i.p.) was administered 30 min before testing, which consisted of a sample phase (5 min), a delay interval (15 min) and a test phase (2 min). DCS treatment reversed scopolamine-induced deficits in discriminatory behavior during the test phase. However, DCS did not affect decreased object exploration itself or increased thigmotaxis in the open-field arena induced by scopolamine. These results support our hypothesis and suggest differential contributions of glutamatergic-cholinergic system interactions to recognition memory and non-mnemonic exploratory behaviors.
14q12q13.2 microdeletion syndrome: Clinical characterization of a new patient, review of the literature, and further evidence of a candidate region for CNS anomalies.
Molecular genetics & genomic medicine, 2020

Chromosome 14q11-q22 deletion syndrome (OMIM 613457) is a rare contiguous gene syndrome. Two regions of overlap (RO) of the 14q12q21.1 deletion have been identified: a proximal region (RO1), including FOXG1(*164874), NKX2-1(*600635), and PAX9(*167416) and a distal region (RO2), including NKX2-1 and PAX9. We report a 6-year-old boy with mild dysmorphic facial features, global developmental delay, and hypoplasia of the corpus callosum.
microRNA 155 up regulation in the CNS is strongly correlated to Down's syndrome dementia.
Annals of diagnostic pathology, 2018

This study examined the molecular correlates of Down's dementia. qRTPCR for chromosome 21 microRNAs was correlated with in situ hybridization, immunohistochemistry for microRNA targets, mRNAs located on chromosome 21, and neurofibrillary tangles in human and the Ts65 dn mouse Down's model. qRTPCR for the microRNAs on the triplicated chromosome showed miR-155 dominance in brain tissues (14.3 fold increase, human and 24.2 fold increase, mouse model) that co-expressed with hyperphosphorylated tau protein. miR-155 was not elevated in Alzheimer's disease or neonates with Downs' syndrome. Chromosome 21 genes APP/BA-42, DYRK1a and BACH1 were not correlated to pathologic changes in Down's dementia. Validated CNS targets of miR-155 that were present in controls and Alzheimer's disease but lacking in Down's dementia brains included BACH1, CoREST1, bcl6, BIM, bcl10, cyclin D, and SAPK4. It is concluded that Down's dementia strongly correlated with overexpression of chromosome 21 microRNA 155 with concomitant reduction of multiple CNS-functional targets. This study highlights the need for anatomic pathologists to determine the specific and diverse pathways cells may take to form neurofibrillary tangles in the different dementias.
Behavioral relevance helps untangle natural vocal categories in a specific subset of core auditory cortical pyramidal neurons.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015

Sound categorization is essential for auditory behaviors like acoustic communication, but its genesis within the auditory pathway is not well understood-especially for learned natural categories like vocalizations, which often share overlapping acoustic features that must be distinguished (e.g., speech). We use electrophysiological mapping and single-unit recordings in mice to investigate how representations of natural vocal categories within core auditory cortex are modulated when one category acquires enhanced behavioral relevance. Taking advantage of a maternal mouse model of acoustic communication, we found no long-term auditory cortical map expansion to represent a behaviorally relevant pup vocalization category-contrary to expectations from the cortical plasticity literature on conditioning with pure tones. Instead, we observed plasticity that improved the separation between acoustically similar pup and adult vocalization categories among a physiologically defined subset of late-onset, putative pyramidal neurons, but not among putative interneurons. Additionally, a larger proportion of these putative pyramidal neurons in maternal animals compared with nonmaternal animals responded to the individual pup call exemplars having combinations of acoustic features most typical of that category. Together, these data suggest that higher-order representations of acoustic categories arise from a subset of core auditory cortical pyramidal neurons that become biased toward the combination of acoustic features statistically predictive of membership to a behaviorally relevant sound category.
Signaling by gasotransmitters.
Science signaling, 2009

Nitric oxide is well established as a major signaling molecule. Evidence is accumulating that carbon monoxide and hydrogen sulfide also are physiologic mediators in the cardiovascular, immune, and nervous systems. This Review focuses on mechanisms whereby they signal by binding to metal centers in metalloproteins, such as in guanylyl cyclase, or modifying sulfhydryl groups in protein targets.
Cost of Parkinson's disease among Filipino patients seen at a public tertiary hospital in Metro Manila.
Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia, 2020

Cost of illness (COI) studies are used to estimate the economic burden of a particular disease. The chronicity of Parkinson's disease (PD) and its lack of treatment make its projected economic burden to grow substantially over the next few decades.
Epigenetic regulation in memory and cognitive disorders.
Neuroscience, 2014

While the importance of epigenetic mechanisms is well established for numerous aspects of cell differentiation and development, recent findings have shown epigenetic processes to be a critical regulatory component in postmitotic neurons. Particularly intriguing, and potentially significant, are data demonstrating epigenetic regulation of cognitive behaviors. Different aspects of learning and memory appear to be regulated at the level of epigenetic chromatin modifications. Furthermore, it is becoming clear that the dysfunction of epigenetic mechanisms can lead to various disorders accompanied by significant mental impairment. Here, we review the evidence for the epigenetic control of cognition and the role of epigenetic dysregulation in mental disorders. A better understanding of epigenetic mechanisms will increase our fundamental knowledge of cognition and also provide new and exciting avenues of treatment for various mental disorders.
Monoamines Inhibit GABAergic Neurons in Ventrolateral Preoptic Area That Make Direct Synaptic Connections to Hypothalamic Arousal Neurons.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2018

The hypothalamus plays an important role in the regulation of sleep/wakefulness states. While the ventrolateral preoptic nucleus (VLPO) plays a critical role in the initiation and maintenance of sleep, the lateral posterior part of the hypothalamus contains neuronal populations implicated in maintenance of arousal, including orexin-producing neurons (orexin neurons) in the lateral hypothalamic area (LHA) and histaminergic neurons in the tuberomammillary nucleus (TMN). During a search for neurons that make direct synaptic contact with histidine decarboxylase-positive (HDC+), histaminergic neurons (HDC neurons) in the TMN and orexin neurons in the LHA of male mice, we found that these arousal-related neurons are heavily innervated by GABAergic neurons in the preoptic area including the VLPO. We further characterized GABAergic neurons electrophysiologically in the VLPO (GABA