rudyvdbrink/CitationDatabase huggingface dataset:
Human bone marrow mesenchymal stem cells protect catecholaminergic and serotonergic neuronal perikarya and transporter function from oxidative stress by the secretion of glial-derived neurotrophic factor.
Brain research, 2012

In neurodegenerative disorders, including Parkinson's disease (PD), the potential of mesenchymal stem cells (MSCs) to produce neurorestoration via trans-differentiation has garnered much interest. We believe, however, that the paracrine effects of MSCs may have greater utility. MSCs release neurotrophic factors, including glial derived neurotrophic factor (GDNF). The benefits conferred by MSC GDNF release could potentially apply to all degenerating monoaminergic fibre types, throughout the brains of patients with PD, rather than solely affording protection to the dopaminergic neurones of the nigro-striatal pathway alone. Using an in vitro approach, we have investigated the neuroprotective properties of unmodified human MSCs on rat catecholaminergic and serotonergic cell cultures exposed to the damaging effects of nitric oxide. We have shown that post oxidative and inflammatory stress, soluble factors produced by native human MSCs, requiring no direct cell-cell contact or genetic or other manipulation, confer protection not only of cultured monoaminergic perikarya, but also of monoamine neurotransmitter transporter function. Furthermore, we have confirmed that, in part, this MSC mediated neuroprotective effect is due to MSC GDNF release and that such protection is diminished when the action of GDNF is blocked. Trophic factor release may afford a way by which intravenously infused MSCs can offer protection to all of the dopaminergic, noradrenergic and serotonergic fibre types degenerating widely throughout the brains of patients with PD.
Mineralocorticoid receptor haplotypes sex-dependently moderate depression susceptibility following childhood maltreatment.
Psychoneuroendocrinology, 2015

The MR is an important regulator of the hypothalamic-pituitary-adrenal (HPA) axis and a prime target for corticosteroids. There is increasing evidence from both clinical and preclinical studies that the MR has different effects on behavior and mood in males and females. To investigate the hypothesis that the MR sex-dependently influences the relation between childhood maltreatment and depression, we investigated three common and functional MR haplotypes (GA, CA, and CG haplotype, based on rs5522 and rs2070951) in a population-based cohort (N = 665) and an independent clinical cohort from the Netherlands Study of Depression and Anxiety (NESDA) (N = 1639). The CA haplotype sex-dependently moderated the relation between childhood maltreatment and depressive symptoms both in the population-based sample (sex × maltreatment × haplotype: β = -4.07, P = 0.029) and in the clinical sample (sex × maltreatment × haplotype, β = -2.40, P = 0.011). Specifically, female individuals in the population-based sample were protected (β = -4.58, P = 2.0 e(-5)), whereas males in the clinical sample were at increased risk (β = 2.54, P = 0.0022). In line with these results, female GA haplotype carriers displayed increased vulnerability in the population-based sample (β = 4.58, P = 7.5 e(-5)) whereas male CG-carriers showed increased resilience in the clinical sample (β = -2.71, P = 0.016). Consistently, we found a decreased lifetime MDD risk for male GA haplotype carriers following childhood maltreatment but an increased risk for male CA haplotype carriers in the clinical sample. In both samples, sex-dependent effects were observed for GA-GA diplotype carriers. In summary, sex plays an important role in determining whether functional genetic variation in MR is beneficial or detrimental, with an apparent female advantage for the CA haplotype but male advantage for the GA and CG haplotype. These sex-dependent effects of MR on depression susceptibility following childhood maltreatment are relevant in light of the increased prevalence of mood disorders in women and point to a sex-specific role of MR in the etiology of depression following childhood maltreatment.
Out of touch with reality? Social perception in first-episode schizophrenia.
Social cognitive and affective neuroscience, 2013

Social dysfunction has been recognized as an elementary feature of schizophrenia, but it remains a crucial issue whether social deficits in schizophrenia concern the inter-subjective domain or primarily have their roots in disturbances of self-experience. Social perception comprises vicarious processes grounding an experiential inter-relationship with others as well as self-regulation processes allowing to maintain a coherent sense of self. The present study investigated whether the functional neural basis underlying these processes is altered in first-episode schizophrenia (FES). Twenty-four FES patients and 22 healthy control participants underwent functional magnetic resonance imaging during a social perception task requiring them to watch videos depicting other individuals' inanimate and animate/social tactile stimulations, and a tactile localizer condition. Activation in ventral premotor cortex for observed bodily tactile stimulations was reduced in the FES group and negatively correlated with self-experience disturbances. Moreover, FES patients showed aberrant differential activation in posterior insula for first-person tactile experiences and observed affective tactile stimulations. These findings suggest that social perception in FES at a pre-reflective level is characterized by disturbances of self-experience, including impaired multisensory representations and self-other distinction. However, the results also show that social perception in FES involves more complex alterations of neural activation at multiple processing levels.
A Pivotal Role for Thiamine Deficiency in the Expression of Neuroinflammation Markers in Models of Alcohol-Related Brain Damage.
Alcoholism, clinical and experimental research, 2019

Alcohol-related brain damage (ARBD) is associated with neurotoxic effects of heavy alcohol use and nutritional deficiency, in particular thiamine deficiency (TD), both of which induce inflammatory responses in brain. Although neuroinflammation is a critical factor in the induction of ARBD, few studies have addressed the specific contribution(s) of ethanol (EtOH) versus TD.
Hair cell overexpression of Islet1 reduces age-related and noise-induced hearing loss.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013

Isl1 is a LIM-homeodomain transcription factor that is critical in the development and differentiation of multiple tissues. In the mouse inner ear, Isl1 is expressed in the prosensory region of otocyst, in young hair cells and supporting cells, and is no longer expressed in postnatal auditory hair cells. To evaluate how continuous Isl1 expression in postnatal hair cells affects hair cell development and cochlear function, we created a transgenic mouse model in which the Pou4f3 promoter drives Isl1 overexpression specifically in hair cells. Isl1 overexpressing hair cells develop normally, as seen by morphology and cochlear functions (auditory brainstem response and otoacoustic emissions). As the mice aged to 17 months, wild-type (WT) controls showed the progressive threshold elevation and outer hair cell loss characteristic of the age-related hearing loss (ARHL) in the background strain (C57BL/6J). In contrast, the Isl1 transgenic mice showed significantly less threshold elevation with survival of hair cells. Further, the Isl1 overexpression protected the ear from noise-induced hearing loss (NIHL): both ABR threshold shifts and hair cell death were significantly reduced when compared with WT littermates. Our model suggests a common mechanism underlying ARHL and NIHL, and provides evidence that hair cell-specific Isl1 expression can promote hair cell survival and therefore minimize the hearing impairment that normally occurs with aging and/or acoustic overexposure.
Structure-Specific and Individual-Dependent Metabolization of Human Milk Oligosaccharides in Infants: A Longitudinal Birth Cohort Study.
Journal of agricultural and food chemistry, 2021

To follow human milk oligosaccharide (HMO) biosynthesis and in vivometabolization, mother milk and infant feces from 68 mother-infant dyads at 2, 6, and 12 weeks postpartum were analyzed, with 18 major HMOs quantitated. Fucosylated and neutral core HMO levels in milk were dependent on mothers' Lewis/Secretor status, whereas most sialylated HMO levels were independent. Infant fecal excretion of HMOs gradually declined with age, especially for neutral core structures. Although decreasing in absolute concentrations in milk during lactation, the relative abundance of total fucosylated HMOs increased in both milk and feces. Mono-fucosylated HMOs were more consumed than those decorated with two fucose moieties. More (α2-3)-sialylated HMOs were degraded than (α2-6)-sialylated HMOs. The transition speed of HMO metabolization from nonspecific or structure-specific consumption stage to the complete consumption stage was individual-dependent. Variation was associated with mode and place of delivery, where caesarean section or early exposure to hospital environment delayed the transition.
Dengue virus dominates lipid metabolism modulations in Wolbachia-coinfected Aedes aegypti.
Communications biology, 2020

Competition between viruses and Wolbachia for host lipids is a proposed mechanism of Wolbachia-mediated virus blocking in insects. Yet, the metabolomic interaction between virus and symbiont within the mosquito has not been clearly defined. We compare the lipid profiles of Aedes aegypti mosquitoes bearing mono- or dual-infections of the Wolbachia wMel strain and dengue virus serotype 3 (DENV3). We found metabolic signatures of infection-induced intracellular events but little evidence to support direct competition between Wolbachia and virus for host lipids. Lipid profiles of dual-infected mosquitoes resemble those of DENV3 mono-infected mosquitoes, suggesting virus-driven modulation dominates over that of Wolbachia. Interestingly, knockdown of key metabolic enzymes suggests cardiolipins are host factors for DENV3 and Wolbachia replication. These findings define the Wolbachia-DENV3 metabolic interaction as indirectly antagonistic, rather than directly competitive, and reveal new research avenues with respect to mosquito × virus interactions at the molecular level.
The potential application of a transcriptionally regulated oncolytic herpes simplex virus for human cancer therapy.
British journal of cancer, 2014

Emerging studies have shown the potential benefit of arming oncolytic viruses with therapeutic genes. However, most of these therapeutic genes are placed under the regulation of ubiquitous viral promoters. Our goal is to generate a safer yet potent oncolytic herpes simplex virus type-1 (HSV-1) for cancer therapy.
Menthol cigarettes: moving toward a broader definition of harm.
Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco, 2010

The current practice of the tobacco industry of primarily focusing on the extent that menthol cigarettes contribute or do not contribute to excess morbidity and mortality in various diseases does not, in and of itself, fully illuminate the harm caused by these products. In fact, this practice actually masks and obscures the public health harm associated with menthol cigarettes. Given this, this commentary develops and presents a broader definition of harm in which to view menthol cigarettes and as the necessary and underlying rationale of why this candy-flavored ingredient should be removed from all tobacco products.
Fibroblast growth factor-2 deficiency causes defects in adult hippocampal neurogenesis, which are not rescued by exogenous fibroblast growth factor-2.
Journal of neuroscience research, 2011

Neurogenesis within the adult brain is restricted to selected areas, one of which is the dentate gyrus (DG). Several growth factors have been reported to affect neurogenesis in the adult DG. However, a role of fibroblast growth factor-2 (FGF-2) in adult hippocampal neurogenesis has not been firmly established. We have analyzed neurogenesis in the DG using in vivo and in vitro approaches. FGF-2(-/-) mice revealed no alterations in the number of proliferating cells but a significant decrease in the numbers of newly generated neurons. Moreover, FGF-2 added to hippocampal slice cultures from FGF-2(-/-) mice was unable to rescue the phenotype. Although an increase in death of neurogenic cells in the FGF-2-deficient DG could not be specifically demonstrated, there was a massive increase in global cell death in FGF-2(-/-) hippocampal slice cultures compared with slices from wild-type mice. Cell death could not be prevented by addition of FGF-2. Neutralization of endogenous FGF-2 in hippocampal slices did not interfere with neurogenesis in a short-term paradigm. Together, our data suggest that FGF-2 is essentially required for maturation of new neurons in adult hippocampal neurogenesis but is likely to operate synergistically in combination with other mechanisms/growth factors.
Intrinsic mechanisms of neuronal axon regeneration.
Nature reviews. Neuroscience, 2018

Permanent disabilities following CNS injuries result from the failure of injured axons to regenerate and rebuild functional connections with their original targets. By contrast, injury to peripheral nerves is followed by robust regeneration, which can lead to recovery of sensory and motor functions. This regenerative response requires the induction of widespread transcriptional and epigenetic changes in injured neurons. Considerable progress has been made in recent years in understanding how peripheral axon injury elicits these widespread changes through the coordinated actions of transcription factors, epigenetic modifiers and, to a lesser extent, microRNAs. Although many questions remain about the interplay between these mechanisms, these new findings provide important insights into the pivotal role of coordinated gene expression and chromatin remodelling in the neuronal response to injury.
Neurological damage disrupts normal sex differences in psychophysiological responsiveness to music.
Psychophysiology, 2016

Men and women often display different physiological responses to emotional stimuli, and these responses can be affected by brain damage. Here, we investigated how brain damage differentially affects electrodermal responses based on sex. We studied neurologically normal, healthy adults and a sample of neurological patients. Participants listened to music, an emotional stimulus that reliably elicits skin conductance responses (SCRs). Electrodermal activity was recorded while participants listened to musical clips. When analyzing the data without regard to sex, there were no differences between healthy and brain-damaged participants in their SCRs. However, we found a significant interaction between brain injury status and sex. For men, brain damage significantly reduced SCRs. For women, there were no differences between brain-damaged participants and neurologically healthy participants. These findings illustrate the importance of including demographic variables, such as sex, when investigating brain-behavior relationships with a psychophysiological dependent variable.
Noradrenergic correlates of chronic cocaine craving: neuromelanin and functional brain imaging.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2021

Preclinical studies have implicated noradrenergic (NA) dysfunction in cocaine addiction. In particular, the NA system plays a central role in motivated behavior and may partake in the regulation of craving and drug use. Yet, human studies of the NA system are scarce, likely hampered by the difficulty in precisely localizing the locus coeruleus (LC). Here, we used neuromelanin imaging to localize the LC and quantified LC neuromelanin signal (NMS) intensity in 44 current cocaine users (CU; 37 men) and 59 nondrug users (NU; 44 men). We also employed fMRI to investigate cue-induced regional responses and LC functional connectivities, as quantified by generalized psychophysiological interaction (gPPI), in CU. Imaging data were processed by published routines and the findings were evaluated with a corrected threshold. We examined how these neural measures were associated with chronic cocaine craving, as assessed by the Cocaine Craving Questionnaire (CCQ). Compared to NU, CU demonstrated higher LC NMS for all probabilistic thresholds defined of 50-90% of the peak. In contrast, NMS of the ventral tegmental area/substantia nigra (VTA/SN) did not show significant group differences. Drug as compared to neutral cues elicited higher activations of many cortical and subcortical regions, none of which were significantly correlated with CCQ score. Drug vs. neutral cues also elicited "deactivation" of bilateral parahippocampal gyri (PHG) and PHG gPPI with a wide array of cortical and subcortical regions, including the ventral striatum and, with small volume correction, the LC. Less deactivation of the PHG (r = 0.40, p = 0.008) and higher PHG-LC gPPI (r = 0.44, p = 0.003) were positively correlated with the CCQ score. In contrast, PHG-VTA/SN connectivity did not correlate with the CCQ score. Together, chronic cocaine exposure may induce higher NMS intensity, suggesting neurotoxic effects on the LC. The correlation of cue-elicited PHG LC connectivity with CCQ score suggests a noradrenergic correlate of chronic cocaine craving. Potentially compensating for memory functions as in neurodegenerative conditions, cue-elicited PHG LC circuit connectivity plays an ill-adaptive role in supporting cocaine craving.
Tissue Antioxidant Status and Lipid Peroxidation Are Related to Dietary Intake of n-3 Polyunsaturated Acids: A Rabbit Model.
Antioxidants (Basel, Switzerland), 2021

Polyunsaturated fatty acid (PUFA) metabolism and tissue distribution is modulated by the oxidation of these molecules. This research aimed to investigate the implication of dietary n-3 PUFA supplementation (precursor and long-chain PUFA) on the PUFA profile and oxidative status of the liver, testis, and brain of adult rabbit bucks. Twenty New Zealand White rabbit bucks were divided into four experimental groups (
Cytomegalovirus promotes murine glioblastoma growth via pericyte recruitment and angiogenesis.
The Journal of clinical investigation, 2019

Cytomegalovirus (CMV) has been implicated in glioblastoma (GBM); however, a mechanistic connection in vivo has not been established. The purpose of this study is to characterize the effects of murine CMV (MCMV) on GBM growth in murine models. Syngeneic GBM models were established in mice perinatally infected with MCMV. We found that tumor growth was markedly enhanced in MCMV+ mice, with a significant reduction in overall survival compared with that of controls (P < 0.001). We observed increased angiogenesis and tumor blood flow in MCMV+ mice. MCMV reactivation was observed in intratumoral perivascular pericytes and tumor cells in mouse and human GBM specimens, and pericyte coverage of tumor vasculature was strikingly augmented in MCMV+ mice. We identified PDGF-D as a CMV-induced factor essential for pericyte recruitment, angiogenesis, and tumor growth. The antiviral drug cidofovir improved survival in MCMV+ mice, inhibiting MCMV reactivation, PDGF-D expression, pericyte recruitment, and tumor angiogenesis. These data show that MCMV potentiates GBM growth in vivo by increased pericyte recruitment and angiogenesis due to alterations in the secretome of CMV-infected cells. Our model provides evidence for a role of CMV in GBM growth and supports the application of antiviral approaches for GBM therapy.
Celsr1 is required for the generation of polarity at multiple levels of the mouse oviduct.
Development (Cambridge, England), 2014

The oviduct is an important organ in reproduction where fertilization occurs, and through which the fertilized eggs are carried to the uterus in mammals. This organ is highly polarized, where the epithelium forms longitudinal folds along the ovary-uterus axis, and the epithelial multicilia beat towards the uterus to transport the ovulated ova. Here, we analyzed the postnatal development of mouse oviduct and report that multilevel polarities of the oviduct are regulated by a planar cell polarity (PCP) gene, Celsr1. In the epithelium, Celsr1 is concentrated in the specific cellular boundaries perpendicular to the ovary-uterus axis from postnatal day 2. We found a new feature of cellular polarity in the oviduct - the apical surface of epithelial cells is elongated along the ovary-uterus axis. In Celsr1-deficient mice, the ciliary motion is not orchestrated along the ovary-uterus axis and the transport ability of beating cilia is impaired. Epithelial cells show less elongation and randomized orientation, and epithelial folds show randomized directionality and ectopic branches in the mutant. Our mosaic analysis suggests that the geometry of epithelial cells is primarily regulated by Celsr1 and as a consequence the epithelial folds are aligned. Taken together, we reveal the characteristics of the multilevel polarity formation processes in the mouse oviduct epithelium and suggest a novel function of the PCP pathway for proper tissue morphogenesis.
Multivariate Analysis of Structural and Functional Neuroimaging Can Inform Psychiatric Differential Diagnosis.
Diagnostics (Basel, Switzerland), 2020

Traditional psychiatric diagnosis has been overly reliant on either self-reported measures (introspection) or clinical rating scales (interviews). This produced the so-called explanatory gap with the bio-medical disciplines, such as neuroscience, which are supposed to deliver biological explanations of disease. In that context the neuro-biological and clinical assessment in psychiatry remained discrepant and incommensurable under conventional statistical frameworks. The emerging field of translational neuroimaging attempted to bridge the explanatory gap by means of simultaneous application of clinical assessment tools and functional magnetic resonance imaging, which also turned out to be problematic when analyzed with standard statistical methods. In order to overcome this problem our group designed a novel machine learning technique, multivariate linear method (MLM) which can capture convergent data from voxel-based morphometry, functional resting state and task-related neuroimaging and the relevant clinical measures. In this paper we report results from convergent cross-validation of biological signatures of disease in a sample of patients with schizophrenia as compared to depression. Our model provides evidence that the combination of the neuroimaging and clinical data in MLM analysis can inform the differential diagnosis in terms of incremental validity.