rudyvdbrink/CitationDatabase huggingface dataset:
Brain proteome changes in female Brd1
Neurobiology of disease, 2019

Genetic and molecular studies have implicated the Bromodomain containing 1 (BRD1) gene in the pathogenesis of schizophrenia and bipolar disorder. Accordingly, mice heterozygous for a targeted deletion of Brd1 (Brd1
Expression of amphetamine sensitization is associated with recruitment of a reactive neuronal population in the nucleus accumbens core.
Psychopharmacology, 2008

Repeated exposure to psychostimulant drugs causes a long-lasting increase in the psychomotor and reinforcing effects of these drugs and an array of neuroadaptations. One such alteration is a hypersensitivity of striatal activity such that a low dose of amphetamine in sensitized animals produces dorsal striatal activation patterns similar to acute treatment with a high dose of amphetamine.
Association of Clinical, Biological, and Brain Magnetic Resonance Imaging Findings With Electroencephalographic Findings for Patients With COVID-19.
JAMA network open, 2021

There is evidence of central nervous system impairments associated with coronavirus disease 2019 (COVID-19) infection, including encephalopathy. Multimodal monitoring of patients with COVID-19 may delineate the specific features of COVID-19-related encephalopathy and guide clinical management.
Nurr1 (NR4A2) regulates Alzheimer's disease-related pathogenesis and cognitive function in the 5XFAD mouse model.
Aging cell, 2019

The orphan nuclear receptor Nurr1 (also known as NR4A2) is critical for the development and maintenance of midbrain dopaminergic neurons, and is associated with Parkinson's disease. However, an association between Nurr1 and Alzheimer's disease (AD)-related pathology has not previously been reported. Here, we provide evidence that Nurr1 is expressed in a neuron-specific manner in AD-related brain regions; specifically, it is selectively expressed in glutamatergic neurons in the subiculum and the cortex of both normal and AD brains. Based on Nurr1's expression patterns, we investigated potential functional roles of Nurr1 in AD pathology. Nurr1 expression was examined in the hippocampus and cortex of AD mouse model and postmortem human AD subjects. In addition, we performed both gain-of-function and loss-of-function studies of Nurr1 and its pharmacological activation in 5XFAD mice. We found that knockdown of Nurr1 significantly aggravated AD pathology while its overexpression alleviated it, including effects on Aβ accumulation, neuroinflammation, and neurodegeneration. Importantly, 5XFAD mice treated with amodiaquine, a highly selective synthetic Nurr1 agonist, showed robust reduction in typical AD features including deposition of Aβ plaques, neuronal loss, microgliosis, and impairment of adult hippocampal neurogenesis, leading to significant improvement of cognitive impairment. These in vivo and in vitro findings suggest that Nurr1 critically regulates AD-related pathophysiology and identify Nurr1 as a novel AD therapeutic target.
Long-term behavioral consequences of prenatal MDMA exposure.
Physiology & behavior, 2009

The current study sought to determine whether prenatal 3,4-methylenedioxy-N-methamphetamine (MDMA) exposure from E14-20 in the rat resulted in behavioral sequelae in adult offspring. Prenatal MDMA exposure results in increased dopaminergic fiber density in the prefrontal cortex, striatum and nucleus accumbens of young rats. Since these areas are critical in response to novelty, reward, attention and locomotor activity, we hypothesized that prenatal MDMA exposure would produce significant changes in the performance of tasks that examine such behaviors in adult rats. Adult rats prenatally exposed to MDMA exhibited greater activity and spent more time in the center during a novel open field test as compared to controls. This increased activity was not reflected in normal home cage activity. Prenatal exposure to MDMA did not affect feeding or food reward. It did not alter cocaine self-administration behaviors, nor did it have an effect on the locomotor response to amphetamine challenge. Finally, while prenatal MDMA did not affect performance in the radial arm maze or the Morris water maze (MWM), these animals demonstrated altered performance in a cued MWM paradigm. Prenatal MDMA exposure resulted in perseverative attendance to a hanging cue when the platform in the MWM was removed as compared to controls. Together, these data demonstrate that prenatal exposure to MDMA results in a behavioral phenotype in adult rats characterized by reduced anxiety, a heightened response to novelty, and "hyperattentiveness" to environmental cues during spatial learning.
Mitochondria in the striatum of subjects with schizophrenia.
The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry, 2011

Schizophrenia is a severe mental illness that manifests pathology in many brain regions, including the striatum. Among the abnormalities in schizophrenia are those related to mitochondria. The present study sought to determine whether the number of mitochondria was affected at the level of the synapse.
Warfarin, but not rivaroxaban, promotes the calcification of the aortic valve in ApoE-/- mice.
Cardiovascular therapeutics, 2018

Vitamin K antagonists, such as warfarin, are known to promote arterial calcification through blockade of gamma-carboxylation of Matrix-Gla-Protein. It is currently unknown whether other oral anticoagulants such as direct inhibitors of Factor Xa can have protective effects on the progression of aortic valve calcification.
Monolithic and Scalable Au Nanorod Substrates Improve PEDOT-Metal Adhesion and Stability in Neural Electrodes.
Advanced healthcare materials, 2018

Poly(3,4-ethylenenedioxythiophene) or PEDOT is a promising candidate for next-generation neuronal electrode materials but its weak adhesion to underlying metallic conductors impedes its potential. An effective method of mechanically anchoring the PEDOT within an Au nanorod (Au-nr) structure is reported and it is demonstrated that it provides enhanced adhesion and overall PEDOT layer stability. Cyclic voltammetry (CV) stress is used to investigate adhesion and stability of spin-cast and electrodeposited PEDOT. The Au-nr adhesion layer permits 10 000 CV cycles of coated PEDOT film in phosphate buffered saline solution without delamination nor significant change of the electrochemical impedance, whereas PEDOT coating film on planar Au electrodes delaminates at or below 1000 cycles. Under CV stress, spin-cast PEDOT on planar Au delaminates, whereas electroplated PEDOT on planar Au encounters surface leaching/decomposition. After 5 weeks of accelerated aging tests at 60 °C, the electrodeposited PEDOT/Au-nr microelectrodes demonstrate a 92% channel survival compared to only 25% survival for spin-cast PEDOT on planar films. Furthermore, after a 10 week chronic implantation onto mouse barrel cortex, PEDOT/Au-nr microelectrodes do not exhibit delamination nor morphological changes, whereas the conventional PEDOT microelectrodes either partially or fully delaminate. Immunohistochemical evaluation demonstrates no or minimal response to the PEDOT implant.
Autosomal Dominantly Inherited Alzheimer Disease: Analysis of genetic subgroups by Machine Learning.
An international journal on information fusion, 2020

Despite subjects with Dominantly-Inherited Alzheimer's Disease (DIAD) represent less than 1% of all Alzheimer's Disease (AD) cases, the Dominantly Inherited Alzheimer Network (DIAN) initiative constitutes a strong impact in the understanding of AD disease course with special emphasis on the presyptomatic disease phase. Until now, the 3 genes involved in DIAD pathogenesis (PSEN1, PSEN2 and APP) have been commonly merged into one group (Mutation Carriers, MC) and studied using conventional statistical analysis. Comparisons between groups using null-hypothesis testing or longitudinal regression procedures, such as the linear-mixed-effects models, have been assessed in the extant literature. Within this context, the work presented here performs a comparison between different groups of subjects by considering the 3 genes, either jointly or separately, and using tools based on Machine Learning (ML). This involves a feature selection step which makes use of ANOVA followed by Principal Component Analysis (PCA) to determine which features would be realiable for further comparison purposes. Then, the selected predictors are classified using a Support-Vector-Machine (SVM) in a nested k-Fold cross-validation resulting in maximum classification rates of 72-74% using PiB PET features, specially when comparing asymptomatic Non-Carriers (NC) subjects with asymptomatic PSEN1 Mutation-Carriers (PSEN1-MC). Results obtained from these experiments led to the idea that PSEN1-MC might be considered as a mixture of two different subgroups including: a first group whose patterns were very close to NC subjects, and a second group much more different in terms of imaging patterns. Thus, using a k-Means clustering algorithm it was determined both subgroups and a new classification scenario was conducted to validate this process. The comparison between each subgroup
ATP13A2/PARK9 regulates endo-/lysosomal cargo sorting and proteostasis through a novel PI(3, 5)P2-mediated scaffolding function.
Human molecular genetics, 2017

ATP13A2 (also called PARK9), is a transmembrane endo-/lysosomal-associated P5 type transport ATPase. Loss-of-function mutations in ATP13A2 result in the Kufor-Rakeb Syndrome (KRS), a form of autosomal Parkinson's disease (PD). In spite of a growing interest in ATP13A2, very little is known about its physiological role in stressed cells. Recent studies suggest that the N-terminal domain of ATP13A2 may hold key regulatory functions, but their nature remains incompletely understood. To this end, we generated a set of melanoma and neuroblastoma cell lines stably overexpressing wild-type (WT), catalytically inactive (D508N) and N-terminal mutants, or shRNA against ATP13A2. We found that under proteotoxic stress conditions, evoked by the proteasome inhibitor Bortezomib, endo-/lysosomal associated full-length ATP13A2 WT, catalytically-inactive or N-terminal fragment mutants, reduced the intracellular accumulation of ubiquitin-conjugated (Ub) proteins, independent of autophagic degradation. In contrast, ATP13A2 silencing increased the intracellular accumulation of Ub-proteins, a pattern also observed in patient-derived fibroblasts harbouring ATP13A2 loss-of function mutations. In treated cells, ATP13A2 evoked endocytic vesicle relocation and increased cargo export through nanovesicles. Expression of an ATP13A2 mutant abrogating PI(3,5)P2 binding or chemical inhibition of the PI(3,5)P2-generating enzyme PIKfyve, compromised vesicular trafficking/nanovesicles export and rescued intracellular accumulation of Ub-proteins in response to proteasomal inhibition. Hence, our study unravels a novel activity-independent scaffolding role of ATP13A2 in trafficking/export of intracellular cargo in response to proteotoxic stress.
Expressional difference, distributions of TGF-β1 in TGF-β1 knock down transgenic mouse, and its possible roles in injured spinal cord.
Experimental biology and medicine (Maywood, N.J.), 2014

Transforming growth factor β1 (TGF-β1) is a multi-functional cytokine implicated in many aspects of mammalian wound healing and scar tissue formation. However, few experiments have so far addressed the potential biological effects of TGF-β1 in the nervous system after injury, in addition to the immune system. In the present study, expressional silencing TGF-β1 was achieved by selecting predesigning hairpins targeting mouse TGF-β1 genes. Four homozygous transgenic offspring were generated and designed as Founder 90, Founder 12, Founder 41 and Founder 46. The down-regulated rates of TGF-β1 in different transgenic mice were also determined. To investigate the potential roles of TGF-β1, we observed changes in the neurological behavior of TGF-β1-knockdown (TGF-β1-kd) mice after spinal cord transection (SCT). Moreover, mRNA levels of inflammatory cytokines, including IL-1, IL-6, IL-10, NF-κB and TNF, were also detected in nucleate cells from blood by real-time PCR. Consequently, different TGF-β1 expressions were detected in multiple tissues, and protein levels of TGF-β1 decreased at different rates relative to that of wild type (WT) ones. The levels of TGF-β1 proteins in TGF-β1-kd mice decreased at most by 57% in Founder 90, which showed a significant recovery in Basso, Beattie, Bresnahan (BBB) scores after SCT compared with that of WT. However, expressions of immune relative genes showed no dramatic difference compared with WT ones. This study is the first to generate TGF-β1 down regulated mice and determine the possible roles of TGF-β1 in vivo in different conditions.
Neural and computational processes underlying dynamic changes in self-esteem.
eLife, 2017

Self-esteem is shaped by the appraisals we receive from others. Here, we characterize neural and computational mechanisms underlying this form of social influence. We introduce a computational model that captures fluctuations in self-esteem engendered by prediction errors that quantify the difference between expected and received social feedback. Using functional MRI, we show these social prediction errors correlate with activity in ventral striatum/subgenual anterior cingulate cortex, while updates in self-esteem resulting from these errors co-varied with activity in ventromedial prefrontal cortex (vmPFC). We linked computational parameters to psychiatric symptoms using canonical correlation analysis to identify an 'interpersonal vulnerability' dimension. Vulnerability modulated the expression of prediction error responses in anterior insula and insula-vmPFC connectivity during self-esteem updates. Our findings indicate that updating of self-evaluative beliefs relies on learning mechanisms akin to those used in learning about others. Enhanced insula-vmPFC connectivity during updating of those beliefs may represent a marker for psychiatric vulnerability.
Latent awareness: Early conscious access to motor preparation processes is linked to the readiness potential.
NeuroImage, 2019

An experience of intention to move accompanies execution of some voluntary actions. The Readiness Potential (RP) is an increasing negativity over motor brain areas prior to voluntary movement. Classical studies suggested that the RP starts before intention is consciously accessed as measured by offline recall-based reports, yet the interpretation of the RP and its temporal relation to awareness of intention remain controversial. We designed a task in which self-paced actions could be interrupted at random times by a visual cue that probed online awareness of intention. Participants were instructed to respond by pressing a key if they felt they were actively preparing a self-paced movement at the time of the cue (awareness report), but to ignore the cue otherwise. We show that an RP-like activity was more strongly present before the cue for probes eliciting awareness reports than otherwise. We further show that recall-based reports of the time of conscious intention are linked to visual attention processes, whereas online reports elicited by a probe are not. Our results suggest that awareness of intention is accessible at relatively early stages of motor preparation and that the RP is specifically associated with this conscious experience.
Systems consolidation and the content of memory.
Neurobiology of learning and memory, 2013

Systems consolidation is the process by which memories become independent of the hippocampus and stored in regions of the neocortex. This process is commonly studied in rodents using context fear conditioning. It is becoming increasingly clear, however, that context memories do not always undergo systems consolidation. To explain this fact, the current review describes a number of factors that determine whether or not context fear can be retrieved without the hippocampus during remote memory tests. These include neurogenesis, the presentation of reminder cues after learning, the quality of the memory that is retrieved during testing and the method that is used to inactivate the hippocampus. Based on these data, we propose that remote context fear memories can be retrieved by either the hippocampus or the neocortex. Tests of memory quality (e.g. context discrimination) can typically be used to determine which system is engaged during retrieval. The same is not true of recently formed context fear memories, which appear to always require the hippocampus during retrieval.
Astrocytes Grown in Alvetex(®) Three Dimensional Scaffolds Retain a Non-reactive Phenotype.
Neurochemical research, 2016

Protocols which permit the extraction of primary astrocytes from either embryonic or postnatal mice are well established however astrocytes in culture are different to those in the mature CNS. Three dimensional (3D) cultures, using a variety of scaffolds may enable better phenotypic properties to be developed in culture. We present data from embryonic (E15) and postnatal (P4) murine primary cortical astrocytes grown on coated coverslips or a 3D polystyrene scaffold, Alvetex. Growth of both embryonic and postnatal primary astrocytes in the 3D scaffold changed astrocyte morphology to a mature, protoplasmic phenotype. Embryonic-derived astrocytes in 3D expressed markers of mature astrocytes, namely the glutamate transporter GLT-1 with low levels of the chondroitin sulphate proteoglycans, NG2 and SMC3. Embryonic astrocytes derived in 3D show lower levels of markers of reactive astrocytes, namely GFAP and mRNA levels of LCN2, PTX3, Serpina3n and Cx43. Postnatal-derived astrocytes show few protein changes between 2D and 3D conditions. Our data shows that Alvetex is a suitable scaffold for growth of astrocytes, and with appropriate choice of cells allows the maintenance of astrocytes with the properties of mature cells and a non-reactive phenotype.
Dynamic imaging reveals that brain-derived neurotrophic factor can independently regulate motility and direction of neuroblasts within the rostral migratory stream.
Neuroscience, 2010

Neuronal precursors generated in the subventricular zone (SVZ) migrate through the rostral migratory stream (RMS) to the olfactory bulb (OB). Although, the mechanisms regulating this migration remain largely unknown. Studies have shown that molecular factors, such as brain-derived neurotrophic factor (BDNF) emanating from the OB, may function as chemoattractants drawing neuroblasts toward their target. To better understand the role of BDNF in RMS migration, we used an acute slice preparation from early postnatal mice to track the tangential migration of GAD65-GFP labeled RMS neuroblasts with confocal time-lapse imaging. By quantifying the cell dynamics using specific directional and motility criteria, our results showed that removal of the OB did not alter the overall directional trajectory of neuroblasts, but did reduce their motility. This suggested that additional guidance factors present locally within the RMS region also contribute to this migration. Here we report that BDNF and its high affinity receptor, tyrosine kinase receptor type 2 (TrkB), are indeed heterogeneously expressed within the RMS at postnatal day 7. By altering BDNF levels within the entire pathway, we showed that reduced BDNF signaling changes both neuroblast motility and direction, while increased BDNF levels changes only motility. Together these data reveal that during this early postnatal period BDNF plays a complex role in regulating both the motility and direction of RMS flow, and that BDNF comes from sources within the RMS itself, as well as from the olfactory bulb.
Task-Dependent Changes in the Large-Scale Dynamics and Necessity of Cortical Regions.
Neuron, 2019

Neural activity throughout the cortex is correlated with perceptual decisions, but inactivation studies suggest that only a small number of areas are necessary for these behaviors. Here we show that the number of required cortical areas and their dynamics vary across related tasks with different cognitive computations. In a visually guided virtual T-maze task, bilateral inactivation of only a few dorsal cortical regions impaired performance. In contrast, in tasks requiring evidence accumulation and/or post-stimulus memory, performance was impaired by inactivation of widespread cortical areas with diverse patterns of behavioral deficits across areas and tasks. Wide-field imaging revealed widespread ramps of Ca
S[+] Apomorphine is a CNS penetrating activator of the Nrf2-ARE pathway with activity in mouse and patient fibroblast models of amyotrophic lateral sclerosis.
Free radical biology & medicine, 2013

Compelling evidence indicates that oxidative stress contributes to motor neuron injury in amyotrophic lateral sclerosis (ALS), but antioxidant therapies have not yet achieved therapeutic benefit in the clinic. The nuclear erythroid 2-related-factor 2 (Nrf2) transcription factor is a key regulator of an important neuroprotective response by driving the expression of multiple cytoprotective genes via its interaction with the antioxidant response element (ARE). Dysregulation of the Nrf2-ARE system has been identified in ALS models and human disease. Taking the Nrf2-ARE pathway as an attractive therapeutic target for neuroprotection in ALS, we aimed to identify CNS penetrating, small molecule activators of Nrf2-mediated transcription in a library of 2000 drugs and natural products. Compounds were screened extensively for Nrf2 activation, and antioxidant and neuroprotective properties in vitro. S[+]-Apomorphine, a receptor-inactive enantiomer of the clinically approved dopamine-receptor agonist (R[-]-apomorphine), was identified as a nontoxic Nrf2 activating molecule. In vivo S[+]-apomorphine demonstrated CNS penetrance, Nrf2 induction, and significant attenuation of motor dysfunction in the SOD1(G93A) transgenic mouse model of ALS. S[+]-apomorphine also reduced pathological oxidative stress and improved survival following an oxidative insult in fibroblasts from ALS patients. This molecule emerges as a promising candidate for evaluation as a potential neuroprotective agent in ALS patients in the clinic.
When ageing meets the blues: Are current antidepressants effective in depressed aged patients?
Neuroscience and biobehavioral reviews, 2015

"I had to wait 110 years to become famous. I wanted to enjoy it as long as possible.", Jeanne Louise Calment (1875-1997). This review summarizes current knowledge of the effects of antidepressant drugs in elderly patients (double-blind placebo (n=27) or active comparator-controlled clinical trials (n=21) indexed in Pubmed in depressed patients aged ≥60) and in aged mice (≥9 months) and middle-aged rats (≥14 months) on depression-related symptoms and cognitive performances. Finally, other potential therapeutic targets for treating depression-related disorders in elderly patients are also addressed (neurogenesis, GABAB receptor, 5-HT4 receptor, mTOR signaling). Overall, the very few published preclinical studies (n=12 in total) in middle-aged and aged rodents seem to suggest that selective serotonin reuptake inhibitors (SSRIs) may be less effective than tricyclic antidepressant drugs (TCAs) in ameliorating depression-like behavior and cognitive functions. On the other hand, results from clinical trials suggest that there is not a marked difference in efficacy and safety profiles of current marketed classes of antidepressant drugs.