rudyvdbrink/CitationDatabase huggingface dataset:
Sex differences in circuits activated by corticotropin releasing factor in rats.
Hormones and behavior, 2018

Women are more likely than men to suffer from psychiatric disorders characterized by corticotropin releasing factor (CRF) hypersecretion, suggesting sex differences in CRF sensitivity. In rodents, sex differences in the sensitivity of specific brain regions to CRF have been identified. However, regions do not work in isolation, but rather form circuits to coordinate distinct responses to stressful events. Here we examined whether CRF activates different circuits in male and female rats. Following central administration of CRF or artificial cerebrospinal fluid (aCSF), neuronal activation in stress-related areas was assessed using cFOS. Functional connectivity was gauged by correlating the number of cFOS-positive cells between regions and then identifying differences within each sex in correlations for aCSF-treated and CRF-treated groups. This analysis revealed that CRF altered different circuits in males and females. As an example, CRF altered correlations involving the dorsal raphe in males and the bed nucleus of the stria terminalis in females, suggesting sex differences in stress-activated circuits controlling mood and anxiety. Next, plasma estradiol and progesterone levels were correlated with cFOS counts in females. Negative correlations between estradiol and neuronal activation in the regions within the extended amygdala were found in CRF-treated, but not aCSF-treated females. This result suggests that estrogens and CRF together modulate the fear and anxiety responses mediated by these regions. Collectively, these studies reveal sex differences in the way brain regions work together in response to CRF. These differences could drive different stress coping strategies in males and females, perhaps contributing to sex biases in psychopathology.
Comparative analysis of decidual and peripheral immune cells and immune-checkpoint molecules during pregnancy in wild-type and PACAP-deficient mice.
American journal of reproductive immunology (New York, N.Y. : 1989), 2018

PACAP is a neuropeptide having a major relevance in the nervous system and in several peripheral organs including those of the reproductive system. PACAP-deficient mice have several morphological, biochemical, behavioral defects, and show reduced fertility. Female reproductive functions such as fertility, mating behavior, maternal behaviors, and implantation alterations have been widely investigated, but no comparative immune analyses are available in pregnant wild-type (WT) and PACAP knockout (KO) mice.
Revisiting the controversial role of salsolinol in the neurobiological effects of ethanol: old and new vistas.
Neuroscience and biobehavioral reviews, 2012

The possible involvement of salsolinol (Sal), an endogenous condensation product of ACD (the first metabolite of ethanol) and dopamine, in the neurochemical basis underlying ethanol action has been repeatedly suggested although it has not been unequivocally established, still being a controversial matter of debate. The main goal of this review is to evaluate the presumed contribution of Sal to ethanol effects summarizing the reported data since the discovery in the 1970s of Sal formation in vitro during ethanol metabolism until the more recent studies characterizing its behavioral and neurochemical effects. Towards this end, we first analyze the production and detection of Sal, in different brain areas, in basal conditions and after alcohol consumption, highlighting its presence in regions especially relevant in regulating ethanol-drinking behaviour and the importance of the newly developed methods to differentiate both enantiomers of Sal which could help to explain some previous negative findings. Afterwards, we review the behavioral and neurochemical studies. Finally, we present and discuss the previous and current enunciated mechanisms of action of Sal in the CNS.
The variability of motor evoked potential latencies in neurosurgical motor mapping by preoperative navigated transcranial magnetic stimulation.
BMC neuroscience, 2017

Recording of motor evoked potentials (MEPs) is used during navigated transcranial magnetic stimulation (nTMS) motor mapping to locate motor function in the human brain. However, factors potentially underlying MEP latency variability in neurosurgical motor mapping are vastly unknown. In the context of this study, one hundred brain tumor patients underwent preoperative nTMS-based motor mapping of the tumor hemisphere between 2010 and 2013. Fourteen predefined predictor variables were recorded, and MEP latencies of abductor pollicis brevis muscle (APB), abductor digiti minimi muscle (ADM), and flexor carpi radialis muscle (FCR) were analyzed using linear mixed-effect multiple regression analysis with the forward step-wise model comparison approach.
Differential Gene Expression in the Human Brain Is Associated with Conserved, but Not Accelerated, Noncoding Sequences.
Molecular biology and evolution, 2017

Previous studies have found that genes which are differentially expressed within the developing human brain disproportionately neighbor conserved noncoding sequences (CNSs) that have an elevated substitution rate in humans and in other species. One explanation for this general association of differential expression with accelerated CNSs is that genes with pre-existing patterns of differential expression have been preferentially targeted by species-specific regulatory changes. Here we provide support for an alternative explanation: genes that neighbor a greater number of CNSs have a higher probability of differential expression and a higher probability of neighboring a CNS with lineage-specific acceleration. Thus, neighboring an accelerated element from any species signals that a gene likely neighbors many CNSs. We extend the analyses beyond the prenatal time points considered in previous studies to demonstrate that this association persists across developmental and adult periods. Examining differential expression between non-neural tissues suggests that the relationship between the number of CNSs a gene neighbors and its differential expression status may be particularly strong for expression differences among brain regions. In addition, by considering this relationship, we highlight a recently defined set of putative human-specific gain-of-function sequences that, even after adjusting for the number of CNSs neighbored by genes, shows a positive relationship with upregulation in the brain compared with other tissues examined.
Can the default-mode network be described with one spatial-covariance network?
Brain research, 2012

The default-mode network (DMN) has become a well accepted concept in cognitive and clinical neuroscience over the last decade, and perusal of the recent literature attests to a stimulating research field of cognitive and diagnostic applications (for example, (Andrews-Hanna et al., 2010; Koch et al., 2010; Sheline et al., 2009a; Sheline et al., 2009b; Uddin et al., 2008; Uddin et al., 2009; Weng et al., 2009; Yan et al., 2009)). However, a formal definition of what exactly constitutes a functional brain network is difficult to come by. In recent contributions, some researchers argue that the DMN is best understood as multiple interacting subsystems (Buckner et al., 2008) and have explored modular components of the DMN that have different functional specialization and could to some extent be identified separately (Fox et al., 2005; Uddin et al., 2009). Such conception of modularity seems to imply an opposite construct of a 'unified whole', but it is difficult to locate proponents of the idea of a DMN who are supplying constraints that can be brought to bear on data in rigorous tests. Our aim in this paper is to present a principled way of deriving a single covariance pattern as the neural substrate of the DMN, test to what extent its behavior tracks the coupling strength between critical seed regions, and investigate to what extent our stricter concept of a network is consistent with the already established findings about the DMN in the literature. We show that our approach leads to a functional covariance pattern whose pattern scores are a good proxy for the integrity of the connections between a medioprefrontal, posterior cingulate and parietal seed regions. Our derived DMN network thus has potential for diagnostic applications that are simpler to perform than computation of pairwise correlational strengths or seed maps.
Impaired sensorimotor integration in focal hand dystonia patients in the absence of symptoms.
Journal of neurology, neurosurgery, and psychiatry, 2010

Functional imaging studies of people with focal hand dystonia (FHD) have indicated abnormal activity in sensorimotor brain regions. Few studies however, have examined FHD during movements that do not provoke symptoms of the disorder. It is possible, therefore, that any differences between FHD and controls are confounded by activity due to the occurrence of symptoms. Thus, in order to characterise impairments in patients with FHD during movements that do not induce dystonic symptoms, we investigated the neural correlates of externally paced finger tapping movements.
The distinct roles of cyclooxygenase-1 and -2 in neuroinflammation: implications for translational research.
Trends in pharmacological sciences, 2009

Cyclooxygenases (COX-1 and COX-2) are key enzymes in the conversion of arachidonic acid to prostaglandins and other lipid mediators. Because it can be induced by inflammatory stimuli, COX-2 has been classically considered as the most appropriate target for anti-inflammatory drugs. However, recent data indicate that COX-2 can mediate neuroprotection and that COX-1 is a major player in the neuroinflammatory process. We discuss the specific contributions of COX-1 and COX-2 in various neurodegenerative diseases and in models of neuroinflammation. We suggest that, owing to its predominant localization in microglia, COX-1 might be the major player in neuroinflammation, whereas COX-2, which is localized in neurons, might have a major role in models in which the neurons are directly challenged. Overall, the benefit of using COX-2 inhibitors should be carefully evaluated and COX-1 preferential inhibitors should be further investigated as a potential therapeutic approach in neurodegenerative diseases with an inflammatory component.
Distribution, nature, and origin of CXCL14-immunoreactive fibers in rat parotid gland.
Neuroscience letters, 2019

The distribution and nature of CXCL14-immunoreactive nerve fibers in salivary glands, especially the parotid gland was immunohistochemically investigated. Furthermore, the origin of parotid CXCL14-immunoreactive nerve fibers was determined by retrograde tracing experiments. CXCL14-immunoreactive nerve fibers were localized in the parotid, submandibular, and sublingual glands, particularly in the parotid gland. Double staining using identical sections revealed that a subpopulation of cells neuropeptide Y (NPY)-containing fibers was immunopositive for CXCL14 in the parotid gland. In the peripheral regions of acinar cells, CXCL14-immunoreactive fibers tended to coexist with NPY; however, perivascular NPY-immunoreactive fibers tended to be immunonegative for CXCL14. Parotid CXCL14-immunoreactive fibers were immunopositive for tyrosine hydroxylase (TH) but immunonegative for choline acetyltransferase and vasoactive intestinal peptide (VIP). After injection of horseradish peroxidase-labeled wheat germ agglutinin (WGA-HRP) in the parotid gland, retrogradely labeled neurons were seen in the superior cervical ganglion (SCG) and otic ganglion. Some of the WGA-immunoreactive somata in the SCG were immunopositive for CXCL14; however, no doubly-labeled somata were noted in the otic ganglion. These results indicate that CXCL14-immunoreactive nerve fibers originate in the SCG, and are sympathetic in nature. The coexistence of CXCL14 with NPY/TH suggests that CXCL14 may be associated with NPY/TH functions as a neuromodulatory chemokine in the parotid gland. The localization of CXCL14 nerve fibers around the acinar cells of the parotid gland indicates its involvement in acinar cell function, but not vasoconstriction.
Arc expression identifies the lateral amygdala fear memory trace.
Molecular psychiatry, 2016

Memories are encoded within sparsely distributed neuronal ensembles. However, the defining cellular properties of neurons within a memory trace remain incompletely understood. Using a fluorescence-based Arc reporter, we were able to visually identify the distinct subset of lateral amygdala (LA) neurons activated during auditory fear conditioning. We found that Arc-expressing neurons have enhanced intrinsic excitability and are preferentially recruited into newly encoded memory traces. Furthermore, synaptic potentiation of thalamic inputs to the LA during fear conditioning is learning-specific, postsynaptically mediated and highly localized to Arc-expressing neurons. Taken together, our findings validate the immediate-early gene Arc as a molecular marker for the LA neuronal ensemble recruited during fear learning. Moreover, these results establish a model of fear memory formation in which intrinsic excitability determines neuronal selection, whereas learning-related encoding is governed by synaptic plasticity.
Measuring subthreshold autistic traits in the general population: Psychometric properties of the Adult Autism Subthreshold Spectrum (AdAS Spectrum) scale.
Psychiatry research, 2019

The Adult Autism Subthreshold Spectrum (AdAS Spectrum) has been developed to assess the wide spectrum of autistic-like clinical and non-clinical features in adults. Nevertheless, its psychometric properties have been analyzed only with clinical individuals so far. This study was aimed at investigating the dimensionality, reliability and validity of the AdAS Spectrum on a non-clinical sample. Participants were 395 Spanish undergraduate students (60% males; mean age of 21.1 years, SD = 2.6), who completed the AdAS Spectrum, the Autism-Spectrum Quotient (AQ), and the Empathy Quotient (EQ). A confirmatory factor analysis supported the seven-factor structure of the questionnaire. Internal consistency was excellent for the total score and acceptable for five factors. Test-retest reliability over a 4-week period was good. Higher AdAS Spectrum scores significantly correlated with higher AQ and lower EQ scores, supporting the validity of the scale. Moreover, participants studying Science/Technology programs did significantly differ from students following Social/Humanities degree courses on all the AdAS Spectrum scores. Overall, findings support the psychometric properties of the AdAS in a non-clinical sample. Future research is needed to further examine the factorial structure and the internal consistency of the scale in larger samples of general population.
Computer Game Play Reduces Intrusive Memories of Experimental Trauma via Reconsolidation-Update Mechanisms.
Psychological science, 2015

Memory of a traumatic event becomes consolidated within hours. Intrusive memories can then flash back repeatedly into the mind's eye and cause distress. We investigated whether reconsolidation-the process during which memories become malleable when recalled-can be blocked using a cognitive task and whether such an approach can reduce these unbidden intrusions. We predicted that reconsolidation of a reactivated visual memory of experimental trauma could be disrupted by engaging in a visuospatial task that would compete for visual working memory resources. We showed that intrusive memories were virtually abolished by playing the computer game Tetris following a memory-reactivation task 24 hr after initial exposure to experimental trauma. Furthermore, both memory reactivation and playing Tetris were required to reduce subsequent intrusions (Experiment 2), consistent with reconsolidation-update mechanisms. A simple, noninvasive cognitive-task procedure administered after emotional memory has already consolidated (i.e., > 24 hours after exposure to experimental trauma) may prevent the recurrence of intrusive memories of those emotional events.
Biallelic mutations in valyl-tRNA synthetase gene VARS are associated with a progressive neurodevelopmental epileptic encephalopathy.
Nature communications, 2019

Aminoacyl-tRNA synthetases (ARSs) function to transfer amino acids to cognate tRNA molecules, which are required for protein translation. To date, biallelic mutations in 31 ARS genes are known to cause recessive, early-onset severe multi-organ diseases. VARS encodes the only known valine cytoplasmic-localized aminoacyl-tRNA synthetase. Here, we report seven patients from five unrelated families with five different biallelic missense variants in VARS. Subjects present with a range of global developmental delay, epileptic encephalopathy and primary or progressive microcephaly. Longitudinal assessment demonstrates progressive cortical atrophy and white matter volume loss. Variants map to the VARS tRNA binding domain and adjacent to the anticodon domain, and disrupt highly conserved residues. Patient primary cells show intact VARS protein but reduced enzymatic activity, suggesting partial loss of function. The implication of VARS in pediatric neurodegeneration broadens the spectrum of human diseases due to mutations in tRNA synthetase genes.
Simultaneous tonic and phasic REM sleep without atonia best predicts early phenoconversion to neurodegenerative disease in idiopathic REM sleep behavior disorder.
Sleep, 2019

Rapid eye movement (REM) sleep without atonia (RWA) is the main polysomnographic feature of idiopathic REM sleep behavior disorder (iRBD) and is considered to be a promising biomarker predicting conversion to manifested synucleinopathy. Besides conventionally evaluated tonic, phasic and any RWA, we took into consideration also periods, when phasic and tonic RWA appeared simultaneously and we called this activity "mixed RWA." The study aimed to evaluate different types of RWA, to reveal the most relevant biomarker to the conversion.
Neural correlates of proactive and reactive inhibition of saccadic eye movements.
Brain imaging and behavior, 2020

Although research on goal-directed, proactive inhibitory control (IC) and stimulus-driven, reactive IC is growing, no previous study has compared proactive IC in conditions of uncertainty with regard to upcoming inhibition to conditions of certain upcoming IC. Therefore, we investigated effects of certainty and uncertainty on behavior and blood oxygen level dependent (BOLD) signal in proactive and reactive IC. In two studies, healthy adults performed saccadic go/no-go and prosaccade/antisaccade tasks. The certainty manipulation had a highly significant behavioral effect in both studies, with inhibitory control being more successful under certain than uncertain conditions on both tasks (p ≤ 0.001). Saccadic go responses were significantly less efficient under conditions of uncertainty than certain responding (p < 0.001). Event-related functional magnetic resonance imaging (fMRI) (one study) revealed a dissociation of certainty- and uncertainty-related proactive inhibitory neural correlates in the go/no-go task, with lateral and medial prefrontal and occipital cortex showing stronger deactivations during uncertainty than during certain upcoming inhibition, and lateral parietal cortex being activated more strongly during certain upcoming inhibition than uncertainty or certain upcoming responding. In the antisaccade task, proactive BOLD effects arose due to stronger deactivations in uncertain response conditions of both tasks and before certain prosaccades than antisaccades. Reactive inhibition-related BOLD increases occurred in inferior parietal cortex and supramarginal gyrus (SMG) in the go/no-go task only. Proactive IC may imply focusing attention on the external environment for encoding salient or alerting events as well as inhibitory mechanisms that reduce potentially distracting neural processes. SMG and inferior parietal cortex may play an important role in both proactive and reactive IC of saccades.
Brainstem neurons that command mammalian locomotor asymmetries.
Nature neuroscience, 2020

Descending command neurons instruct spinal networks to execute basic locomotor functions, such as gait and speed. The command functions for gait and speed are symmetric, implying that a separate unknown system directs asymmetric movements, including the ability to move left or right. In the present study, we report that Chx10-lineage reticulospinal neurons act to control the direction of locomotor movements in mammals. Chx10 neurons exhibit mainly ipsilateral projection, and their selective unilateral activation causes ipsilateral turning movements in freely moving mice. Unilateral inhibition of Chx10 neurons causes contralateral turning movements. Paired left-right motor recordings identified distinct mechanisms for directional movements mediated via limb and axial spinal circuits. Finally, we identify sensorimotor brain regions that project on to Chx10 reticulospinal neurons, and demonstrate that their unilateral activation can impart left-right directional commands. Together these data identify the descending motor system that commands left-right locomotor asymmetries in mammals.
Oligodendrocyte Regeneration and CNS Remyelination Require TACE/ADAM17.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015

The identification of the molecular network that supports oligodendrocyte (OL) regeneration under demyelinating conditions has been a primary goal for regenerative medicine in demyelinating disorders. We recently described an essential function for TACE/ADAM17 in regulating oligodendrogenesis during postnatal myelination, but it is unknown whether this protein also plays a role in OL regeneration and remyelination under demyelinating conditions. By using genetic mouse models to achieve selective gain- or loss-of-function of TACE or EGFR in OL lineage cells in vivo, we found that TACE is critical for EGFR activation in OLs following demyelination, and therefore, for sustaining OL regeneration and CNS remyelination. TACE deficiency in oligodendrocyte progenitor cells following demyelination disturbs OL lineage cell expansion and survival, leading to a delay in the remyelination process. EGFR overexpression in TACE deficient OLs in vivo restores OL development and postnatal CNS myelination, but also OL regeneration and CNS remyelination following demyelination. Our study reveals an essential function of TACE in supporting OL regeneration and CNS remyelination that may contribute to the design of new strategies for therapeutic intervention in demyelinating disorders by promoting oligodendrocyte regeneration and myelin repair.
Tamoxifen in combination with temozolomide induce a synergistic inhibition of PKC-pan in GBM cell lines.
Biochimica et biophysica acta, 2015

Glioblastoma (GBM) is a highly proliferative, angiogenic grade IV astrocytoma that develops resistance to the alkylating agents used in chemotherapy, such as temozolomide (TMZ), which is considered the gold standard. The mean survival time for GBM patients is approximately 12 months, increasing to 14.6 months after TMZ treatment. The resistance of GBM to chemotherapy seems to be associated to genetic alterations and to the constitutive activation of several signaling pathways. Therefore, the combination of different drugs with different mechanisms of action may contribute to circumvent the chemoresistance of glioma cells. Here we describe the potential synergistic behavior of the therapeutic combination of tamoxifen (TMX), a known inhibitor of PKC, and TMZ in GBM.
Neuroprotective activity and acetylcholinesterase inhibition of five Amaryllidaceae species: a comparative study.
Life sciences, 2015

Amaryllidaceae alkaloids exhibit a wide range of physiological effects, of which the acetylcholinesterase (AChE) inhibitory activity is the most relevant. However, scientific evidence related to their neuroprotective effectiveness against glutamate-induced toxicity has been lacking. Thus, the purpose of this study was to conduct a comparative study of the neuroprotective activity and the AChE inhibitory activity of species of Amaryllidaceae.