rudyvdbrink/CitationDatabase huggingface dataset:
PARP-1-regulated TNF-α expression in the dorsal root ganglia and spinal dorsal horn contributes to the pathogenesis of neuropathic pain in rats.
Brain, behavior, and immunity, 2020

Emerging evidence has implicated poly-(ADP-ribose) polymerase 1 (PARP-1), a transcriptional coregulator, in a variety of inflammatory diseases. In the current study, the role of PARP-1 in neuropathic pain and the underlying mechanisms were investigated. Neuropathic pain was determined by assessing the paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) following lumbar 5 spinal nerve ligation (SNL) in male rates. Western blotting, qRT-PCR, immunohistochemistry, chromatin immunoprecipitation (ChIP), and Co-IP assays were performed to elucidate the mechanisms. The results showed that SNL resulted in a significant increase in the expression and activation of PARP-1 in the ipsilateral L4/5 dorsal root ganglia (DRG) and spinal dorsal horn, which occurred on day one, reached peak on day 7, and persisted more than 2 weeks after surgery. Double immunofluorescence staining revealed that PARP-1 was expressed exclusively in DRG A-type and C-type neurons. In the spinal cord, PARP-1 mainly colocalized with the neuronal marker NeuN and the astrocytic marker GFAP specifically in the superficial lamina. Prior intrathecal (i.t.) injection of PJ-34, a PARPs inhibitor, or Tiq-A, a specific PARP-1 inhibitor, dose-dependently prevented the reductions in PWT and PWL following SNL. Established neuropathic pain-like hypersensitivity was also attenuated with i.t. injection of PJ-34 and Tiq-A starting on day 7 following SNL, a timepoint at which neuropathic pain was fully established. SNL-induced mechanical allodynia and thermal hyperalgesia were also alleviated by i.t. injection of PARP-1 siRNA following a reduction in PARP-1 expression in the dorsal horn. Moreover, the SNL-induced increases in TNF-α protein and mRNA in the dorsal horn and DRG were dramatically suppressed by i.t. injection of Tiq-A or PARP-1 siRNA. The i.t. lipopolysaccharide (LPS)-induced increase in the production of TNF-α in the dorsal horn was also inhibited by prior to i.t. injection of PARP-1 siRNA. Results of ChIP assay showed that SNL-induced PARP-1 activation promoted the binding of NF-κB p65 with the TNF-α promoter in the dorsal horn and that PARP-1 inhibition reduced this binding and suppressed TNF-α expression. Co-IP assay revealed that SNL caused a significant increase in the level of histone H1 poly(ADP)-ribosylation. Together, these results indicate that PARP-1-regulated TNF-α expression in the DRG and spinal dorsal horn following SNL contributes to the development and maintenance of neuropathic pain. Targeting PARP-1 might be a promising therapeutic strategy for the treatment of the chronic pain.
Roles of activated astrocytes in bone marrow stromal cell proliferation and differentiation.
Neuroscience, 2009

Local microenvironment plays an important role in determining the fate choice of stem cells in the central nervous system (CNS). Astrocytes, a major component of local microenvironment in the CNS, have been demonstrated to influence the proliferation and neural differentiation of stem cells including neural stem/progenitor cells, embryonic stem cells and bone marrow stromal cells (BMSCs). However, it has remained to be ascertained if inflammation-activated astrocytes can affect the behavior of BMSCs. To this end, astrocyte-conditioned medium (ACM) was prepared in this study for treatment of BMSCs. The ACM derived from Wistar rat astrocytes stimulated by lipopolysaccharide for 12, 36 or 72 h, respectively, served as inflammatory ACM (12 h ACM, 36 h ACM and 72 h ACM), while that from unstimulated astrocytes was used as normal control astrocyte-conditioned medium (N-ACM). The results showed that the proliferation and neural differentiation of BMSCs grown in inflammatory ACM were significantly increased compared with those grown in N-ACM. The efficiency of BMSCs exposed to 36 h ACM was significantly greater than that of those exposed to 12 or 72 h ACM. Following neutralization of interleukin-6 (IL-6) of the ACM, both the proliferation and astrocytic differentiation of BMSCs were decreased; on the other hand, the neuronal differentiation was significantly increased. The present findings suggest that inflammation-activated astrocytes can facilitate the proliferation and neural differentiation of BMSCs and activated astrocytes at different phase after CNS injuries might have distinct effects on BMSCs. Moreover, astrocyte-derived IL-6 participates in the proliferation and neural differentiation of BMSCs.
Genome-wide association analysis of hippocampal volume identifies enrichment of neurogenesis-related pathways.
Scientific reports, 2019

Adult neurogenesis occurs in the dentate gyrus of the hippocampus during adulthood and contributes to sustaining the hippocampal formation. To investigate whether neurogenesis-related pathways are associated with hippocampal volume, we performed gene-set enrichment analysis using summary statistics from a large-scale genome-wide association study (N = 13,163) of hippocampal volume from the Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Consortium and two year hippocampal volume changes from baseline in cognitively normal individuals from Alzheimer's Disease Neuroimaging Initiative Cohort (ADNI). Gene-set enrichment analysis of hippocampal volume identified 44 significantly enriched biological pathways (FDR corrected p-value < 0.05), of which 38 pathways were related to neurogenesis-related processes including neurogenesis, generation of new neurons, neuronal development, and neuronal migration and differentiation. For genes highly represented in the significantly enriched neurogenesis-related pathways, gene-based association analysis identified TESC, ACVR1, MSRB3, and DPP4 as significantly associated with hippocampal volume. Furthermore, co-expression network-based functional analysis of gene expression data in the hippocampal subfields, CA1 and CA3, from 32 normal controls showed that distinct co-expression modules were mostly enriched in neurogenesis related pathways. Our results suggest that neurogenesis-related pathways may be enriched for hippocampal volume and that hippocampal volume may serve as a potential phenotype for the investigation of human adult neurogenesis.
Introduction to the special issue: The WHO World Mental Health International College Student (WMH-ICS) initiative.
International journal of methods in psychiatric research, 2019

Most mental disorders have their first onset in early adulthood. Epidemiological research, as well as research on preventive and early interventions, is therefore very important. This thematic issue focuses on one of the first systematic attempts to develop such services for college students. The WHO World Mental Health International College Student (WMH-ICS) initiative is based on the largest and continuously growing epidemiological dataset ever collected in college students. Based on these results, the initiative has now started to implement internet-based interventions for common mental disorders and emotional problems. In this special issue, a general paper about the initiative is presented, as well as a paper on the implementation of the WMH-ICS initiative in low and middle income countries. It also includes several papers with core epidemiological results of the initiative, a meta-analysis of internet-based interventions for mental health problems in college students and the first results of trials conducted as part of the initiative. Taken together, the papers in this special issue show that WMH-ICS is on its way to becoming a major initiative in addressing the problem of unmet need for treatment of mental health problems among college students.
Optic pathway-hypothalamic glioma hemorrhage: a series of 9 patients and review of the literature.
Journal of neurosurgery, 2018

OBJECTIVEHemorrhage (also known as apoplexy) in optic pathway gliomas (OPGs) is rare. Because of the variable presentations and low incidence of OPG hemorrhages, little is known about their clinical course and the best treatment options. The aim of this work was to review risk factors, clinical course, and treatment strategies of optic glioma hemorrhages in the largest possible number of cases.METHODSA total of 34 patients were analyzed. Nine new cases were collected, and 25 were identified in the literature. Data regarding demographics, radiological and histological features, treatment, and outcome were retrospectively reviewed.RESULTSThe majority of patients were younger than 20 years. Only 3 patients were known to have neurofibromatosis. The histopathological diagnosis was pilocytic astrocytoma in the majority of cases. Five patients had intraorbital hemorrhages, whereas 29 patients had intracranial hemorrhage; the majority of intracranial bleeds were treated surgically. Six patients, all with intracranial hemorrhage, died due to recurrent bleeding, hydrocephalus, or surgical complications. No clear risk factors could be identified.CONCLUSIONSIntracerebral OPG hemorrhages have a fatal outcome in 20% of cases. Age, hormonal status, neurofibromatosis involvement, and histopathological diagnosis have been suggested as risk factors for hemorrhage, but this cannot be reliably established from the present series. The goals of surgery should be patient survival and prevention of further neurological and ophthalmological deterioration.
Huntington's disease is a four-repeat tauopathy with tau nuclear rods.
Nature medicine, 2014

An imbalance of tau isoforms containing either three or four microtubule-binding repeats causes frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) in families with intronic mutations in the MAPT gene. Here we report equivalent imbalances at the mRNA and protein levels and increased total tau levels in the brains of subjects with Huntington's disease (HD) together with rod-like tau deposits along neuronal nuclei. These tau nuclear rods show an ordered filamentous ultrastructure and can be found filling the neuronal nuclear indentations previously reported in HD brains. Finally, alterations in serine/arginine-rich splicing factor-6 coincide with tau missplicing, and a role of tau in HD pathogenesis is evidenced by the attenuation of motor abnormalities of mutant HTT transgenic mice in tau knockout backgrounds.
Normative biometry of the fetal brain using magnetic resonance imaging.
Brain structure & function, 2017

The fetal brain shows accelerated growth in the latter half of gestation, and these changes can be captured by 2D and 3D biometry measurements. The aim of this study was to quantify brain growth in normal fetuses using Magnetic Resonance Imaging (MRI) and to produce reference biometry data and a freely available centile calculator ( https://www.developingbrain.co.uk/fetalcentiles/ ). A total of 127 MRI examinations (1.5 T) of fetuses with a normal brain appearance (21-38 gestational weeks) were included in this study. 2D and 3D biometric parameters were measured from slice-to-volume reconstructed images, including 3D measurements of supratentorial brain tissue, lateral ventricles, cortex, cerebellum and extra-cerebral CSF and 2D measurements of brain biparietal diameter and fronto-occipital length, skull biparietal diameter and occipitofrontal diameter, head circumference, transverse cerebellar diameter, extra-cerebral CSF, ventricular atrial diameter, and vermis height, width, and area. Centiles were constructed for each measurement. All participants were invited for developmental follow-up. All 2D and 3D measurements, except for atrial diameter, showed a significant positive correlation with gestational age. There was a sex effect on left and total lateral ventricular volumes and the degree of ventricular asymmetry. The 5th, 50th, and 95th centiles and a centile calculator were produced. Developmental follow-up was available for 73.1% of cases [mean chronological age 27.4 (±10.2) months]. We present normative reference charts for fetal brain MRI biometry at 21-38 gestational weeks. Developing growth trajectories will aid in the better understanding of normal fetal brain growth and subsequently of deviations from typical development in high-risk pregnancies or following premature delivery.
Midkine regulates amphetamine-induced astrocytosis in striatum but has no effects on amphetamine-induced striatal dopaminergic denervation and addictive effects: functional differences between pleiotrophin and midkine.
Neuroscience, 2011

Midkine (MK), a neurotrophic factor with important roles in survival and differentiation of dopaminergic neurons, is upregulated in different brain areas after administration of different drugs of abuse suggesting MK could modulate drugs of abuse-induced pharmacological or neuroadaptative effects. To test this hypothesis, we have studied the effects of amphetamine administration in MK genetically deficient (MK-/-) and wild-type (MK+/+) mice. In conditioning studies, we found that amphetamine induces conditioned place preference (CPP) similarly in both MK-/- and MK+/+ mice. In immunohistochemistry studies, we found that amphetamine (10 mg/kg, four times, every 2 h) causes a similar striatal dopaminergic denervation in both MK-/- and MK+/+ mice. However, we detected a significant increase of glial fibrillary acidic protein (GFAP)-positive cells in the striatum of amphetamine-treated MK-/- mice compared to MK+/+ mice, suggesting an enhanced amphetamine-induced astrocytosis in absence of endogenous MK. Interestingly, the levels of expression of the MK receptor, receptor protein tyrosine phosphatase (RPTP) β/ζ, in the striatum were not found to be changed by the drug administration or the mouse genotype. In a similar manner the phosphorylation levels of RPTP β/ζ substrates with important roles in survival of dopaminergic neurons, Fyn kinase and TrkA, and of the MAP kinases ERK1/2, were unaffected by the drug or the genotype. The data clearly suggest that endogenous MK limits amphetamine-induced astrocytosis through Fyn-, TrkA- and ERK1/2-independent mechanisms and identify previously unexpected functional differences between MK and pleiotrophin, the only other member of the MK family of growth factors, in the modulation of effects of drugs of abuse.
Maternal and post-natal obesity alters long-term memory and hippocampal molecular signaling of male rat.
Brain research, 2019

The aim of this study was to investigate whether maternal cafeteria ingestion interferes with long-term memory-related behaviors and hippocampal brain-derived neurotrophic factor (BDNF) signaling in the offspring, and if there is a cumulative effect with the exposure to cafeteria diet during the life-course of the pups. Female rats were fed a control (CON, n = 20) or cafeteria diet (CAF, n = 24) from their weaning to weaning of their offspring. After that, their male offspring were divided into 4 groups (CON-CON, n = 36; CON-CAF, n = 38, CAF-CON, n = 46 and CAF-CAF, n = 39) so that all litters ingested CON or CAF, irrespective of maternal diet. At 30 days of age, all groups exposed to cafeteria diet at some stage in life showed a decline in performance on one or both object recognition and inhibitory avoidance tasks. At 120 days, CON-CAF and CAF-CAF groups continued to show memory impairment. There were no significant differences between groups in the hippocampal concentrations of BDNF and cAMP Response Element Binding protein (CREB) in puberty or adulthood, but the concentration of hippocampal Ras-Raf-MEK-mitogen-activated protein kinase (MAPK) was higher in CAF-CAF pubescent offspring when compared to the CON-CON group. These data suggest that maternal diet affects the behavior and the molecular signaling related to long-term memory of the offspring, and that its effects are influenced by postnatal diet.
Long-term enhancement of brain function and cognition using cognitive training and brain stimulation.
Current biology : CB, 2013

Noninvasive brain stimulation has shown considerable promise for enhancing cognitive functions by the long-term manipulation of neuroplasticity. However, the observation of such improvements has been focused at the behavioral level, and enhancements largely restricted to the performance of basic tasks. Here, we investigate whether transcranial random noise stimulation (TRNS) can improve learning and subsequent performance on complex arithmetic tasks. TRNS of the bilateral dorsolateral prefrontal cortex (DLPFC), a key area in arithmetic, was uniquely coupled with near-infrared spectroscopy (NIRS) to measure online hemodynamic responses within the prefrontal cortex. Five consecutive days of TRNS-accompanied cognitive training enhanced the speed of both calculation- and memory-recall-based arithmetic learning. These behavioral improvements were associated with defined hemodynamic responses consistent with more efficient neurovascular coupling within the left DLPFC. Testing 6 months after training revealed long-lasting behavioral and physiological modifications in the stimulated group relative to sham controls for trained and nontrained calculation material. These results demonstrate that, depending on the learning regime, TRNS can induce long-term enhancement of cognitive and brain functions. Such findings have significant implications for basic and translational neuroscience, highlighting TRNS as a viable approach to enhancing learning and high-level cognition by the long-term modulation of neuroplasticity.
Theta oscillations reflect the dynamics of interference in episodic memory retrieval.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010

Selectively retrieving episodic information from a cue often induces interference from related episodes. To promote successful retrieval of the target episode, such interference is resolved by inhibition, causing retrieval-induced forgetting of the related but irrelevant information. Passively studying the episodic information again (reexposure) does not show this effect. This study examined the hypothesis that brain oscillations in the theta band (5-9 Hz) reflect the dynamics of interference in selective memory retrieval, analyzing EEG data from 24 healthy human subjects (21 women, 3 men). High versus low levels of interference were investigated by comparing the effects of selective retrieval with the effects of reexposure of material, with the former, but not the latter, inducing interference. Moreover, we analyzed repeated cycles of selective retrieval and reexposure, assuming that interference is reduced by inhibition across retrieval cycles, but not across reexposure cycles. We found greater theta band activity in selective retrieval than in reexposure, and a reduction in theta amplitude from the first to the second cycle of retrieval predicting the amount of retrieval-induced forgetting; the sources of theta amplitude reduction across retrieval cycles were located in the anterior cingulate cortex. No difference in theta activity was found across repeated cycles of reexposure. The results suggest that higher levels of interference in episodic memory are indexed by more theta band activity, and that successful interference resolution via inhibition causes a reduction in theta amplitude. Thus, theta band activity can serve as a neural marker of the dynamics of interference in selective episodic retrieval.
Visceral motor neuron diversity delineates a cellular basis for nipple- and pilo-erection muscle control.
Nature neuroscience, 2016

Despite the variety of physiological and target-related functions, little is known regarding the cellular complexity in the sympathetic ganglion. We explored the heterogeneity of mouse stellate and thoracic ganglia and found an unexpected variety of cell types. We identified specialized populations of nipple- and pilo-erector muscle neurons. These neurons extended axonal projections and were born among other neurons during embryogenesis, but remained unspecialized until target organogenesis occurred postnatally. Target innervation and cell-type specification was coordinated by an intricate acquisition of unique combinations of growth factor receptors and the initiation of expression of concomitant ligands by the nascent erector muscles. Overall, our results provide compelling evidence for a highly sophisticated organization of the sympathetic nervous system into discrete outflow channels that project to well-defined target tissues and offer mechanistic insight into how diversity and connectivity are established during development.
Human EEG uncovers latent generalizable rule structure during learning.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014

Human cognition is flexible and adaptive, affording the ability to detect and leverage complex structure inherent in the environment and generalize this structure to novel situations. Behavioral studies show that humans impute structure into simple learning problems, even when this tendency affords no behavioral advantage. Here we used electroencephalography to investigate the neural dynamics indicative of such incidental latent structure. Event-related potentials over lateral prefrontal cortex, typically observed for instructed task rules, were stratified according to individual participants' constructed rule sets. Moreover, this individualized latent rule structure could be independently decoded from multielectrode pattern classification. Both neural markers were predictive of participants' ability to subsequently generalize rule structure to new contexts. These EEG dynamics reveal that the human brain spontaneously constructs hierarchically structured representations during learning of simple task rules.
Dendritic spine actin dynamics in neuronal maturation and synaptic plasticity.
Cytoskeleton (Hoboken, N.J.), 2016

The majority of the postsynaptic terminals of excitatory synapses in the central nervous system exist on small bulbous structures on dendrites known as dendritic spines. The actin cytoskeleton is a structural element underlying the proper development and morphology of dendritic spines. Synaptic activity patterns rapidly change actin dynamics, leading to morphological changes in dendritic spines. In this mini-review, we will discuss recent findings on neuronal maturation and synaptic plasticity-induced changes in the dendritic spine actin cytoskeleton. We propose that actin dynamics in dendritic spines decrease through actin filament crosslinking during neuronal maturation. In long-term potentiation, we evaluate the model of fast breakdown of actin filaments through severing and rebuilding through polymerization and later stabilization through crosslinking. We will discuss the role of Ca(2+) in long-term depression, and suggest that actin filaments are dissolved through actin filament severing. © 2016 Wiley Periodicals, Inc.