rudyvdbrink/CitationDatabase huggingface dataset:
Effects of isoflurane and alpha-chloralose anesthesia on BOLD fMRI responses to ingested L-glutamate in rats.
Neuroscience, 2010

It is important to investigate the effect of anesthesia on blood oxygenation level-dependent (BOLD) signals in an animal model. Many researchers have investigated the BOLD response to visual, sensory, and chemical stimuli in anesthetized rats. There are no reports, however, comparing the differences in the BOLD signal change between anesthetized and conscious rats when a visceral nutrient signal arises. Here, using functional magnetic resonance imaging (fMRI), we investigated the differences in the BOLD signal changes after intragastric administration of l-glutamate (Glu) under three anesthesia conditions: conscious, alpha-chloralose-anesthetized, and isoflurane-anesthetized condition. Under the conscious and alpha-chloralose condition, we observed the significant BOLD signal increase in the medial prefrontal cortex (mPFC), insular cortex (IC), hippocampus, and several hypothalamic regions including the lateral and ventromedial nucleus. In chloralose group, however, gut Glu stimulation induced BOLD signal increase in the prelimbic cortex and orbital cortex, which did not activate in conscious condition. Meanwhile, under isoflurane-anesthetized condition, we did not observe the BOLD signal increase in these areas. BOLD signal intensity in the nucleus of the solitary tract (NTS), to which vagus nerve transmits the visceral information from the gastrointestinal tract, increased in all conditions. Importantly, under conscious condition, we observed increased BOLD signal intensity in several regions related to the metabolic state (i.e. hunger or satiety), such as the mPFC, ventromedial and lateral hypothalamus (LH). Our results suggest that alpha-chloralose and isoflurane anesthesia caused distinct effects on BOLD response to the gut l-Glu stimulation in several brain regions.
Predicting word reading and comprehension with executive function and speed measures across development: a latent variable analysis.
Journal of experimental psychology. General, 2012

The present study explored whether different executive control and speed measures (working memory, inhibition, processing speed, and naming speed) independently predict individual differences in word reading and reading comprehension. Although previous studies suggest these cognitive constructs are important for reading, the authors analyze the constructs simultaneously to test whether each is a unique predictor. Latent variables from 483 participants (ages 8-16 years) were used to portion each cognitive and reading construct into its unique and shared variance. In these models 2 specific issues are addressed: (a) Given that the wide age range may span the theoretical transition from "learning to read" to "reading to learn," the authors first test whether the relation between word reading and reading comprehension is stable across 2 age groups (ages 8-10 and 11-16); and (b) the main theoretical question of interest: whether what is shared and what is separable for word reading and reading comprehension are associated with individual differences in working memory, inhibition, and measures of processing and naming speed. The results indicated that (a) the relation between word reading and reading comprehension is largely invariant across the age groups, and (b) working memory and general processing speed, but not inhibition or the speeded naming of non-alphanumeric stimuli, are unique predictors of both word reading and comprehension, with working memory equally important for both reading abilities and processing speed more important for word reading. These results have implications for understanding why reading comprehension and word reading are highly correlated yet separable
Long-term remission with rituximab in refractory leucine-rich glioma inactivated 1 antibody encephalitis.
Journal of neuroimmunology, 2014

Autoimmune encephalitis associated with antibodies to leucine-rich glioma inactivated 1 (LGI1) is recently described and there is a lack of detailed reports on the treatment of relapsing or refractory cases and long-term outcomes. Two case reports are presented. Both cases had faciobrachial dystonic seizures (FBDS) and received rituximab after relapsing or refractory disease. Both cases achieved sustained clinical remission of up to 15 and 56 months respectively. Rituximab use allowed withdrawal of corticosteroids and was well tolerated. Randomized clinical trials are needed in LGI1 encephalitis and other autoimmune encephalitides.
Repetitive element transcripts are elevated in the brain of C9orf72 ALS/FTLD patients.
Human molecular genetics, 2017

Significant transcriptome alterations are detected in the brain of patients with amyotrophic lateral sclerosis (ALS), including carriers of the C9orf72 repeat expansion and C9orf72-negative sporadic cases. Recently, the expression of repetitive element transcripts has been associated with toxicity and, while increased repetitive element expression has been observed in several neurodegenerative diseases, little is known about their contribution to ALS. To assess whether aberrant expression of repetitive element sequences are observed in ALS, we analysed RNA sequencing data from C9orf72-positive and sporadic ALS cases, as well as healthy controls. Transcripts from multiple classes and subclasses of repetitive elements (LINEs, endogenous retroviruses, DNA transposons, simple repeats, etc.) were significantly increased in the frontal cortex of C9orf72 ALS patients. A large collection of patient samples, representing both C9orf72 positive and negative ALS, ALS/FTLD, and FTLD cases, was used to validate the levels of several repetitive element transcripts. These analyses confirmed that repetitive element expression was significantly increased in C9orf72-positive compared to C9orf72-negative or control cases. While previous studies suggest an important link between TDP-43 and repetitive element biology, our data indicate that TDP-43 pathology alone is insufficient to account for the observed changes in repetitive elements in ALS/FTLD. Instead, we found that repetitive element expression positively correlated with RNA polymerase II activity in postmortem brain, and pharmacologic modulation of RNA polymerase II activity altered repetitive element expression in vitro. We conclude that increased RNA polymerase II activity in ALS/FTLD may lead to increased repetitive element transcript expression, a novel pathological feature of ALS/FTLD.
Acute on chronic exposure to endotoxin is associated with enhanced chemoreflex responses in preterm fetal sheep.
American journal of physiology. Regulatory, integrative and comparative physiology, 2013

There is increasing evidence that exposure to infection can sensitize the fetus to subsequent hypoxic injury. However, it is unclear whether this involves compromise of the fetal cardiovascular adaptation to acute asphyxia. Chronically instrumented 103-day-old (0.7 gestational age, term is 147 days) fetal sheep in utero were randomized to receive either gram-negative lipopolysaccharide (LPS) as a continuous low-dose infusion for 120 h plus boluses of 1 μg LPS at 48, 72, and 96 h with asphyxia at 102 h (i.e., 6 h after the final LPS bolus) induced by umbilical cord occlusion for 15 min (LPS treated, n = 8), or the same volume of saline plus occlusion (saline treated, n = 7). Fetuses were killed 5 days after occlusion. LPS was associated with a more rapid fall in fetal heart rate at the onset of occlusion (P < 0.05) and with minimally lower values during occlusion (P < 0.05). The LPS-treated fetuses had lower fetal mean arterial blood pressure (BP) and greater carotid artery blood flow (CaBF) before occlusion (P < 0.05) but showed an increase in BP and fall in CaBF to similar values as saline controls during occlusion. There were no differences between the groups in femoral blood flow before or during occlusion. Contrary to our initial hypothesis, acute on chronic exposure to LPS was associated with more rapid cardiovascular adaptation to umbilical cord occlusion.
Predicted molecular signaling guiding photoreceptor cell migration following transplantation into damaged retina.
Scientific reports, 2016

To replace photoreceptors lost to disease or trauma and restore vision, laboratories around the world are investigating photoreceptor replacement strategies using subretinal transplantation of photoreceptor precursor cells (PPCs) and retinal progenitor cells (RPCs). Significant obstacles to advancement of photoreceptor cell-replacement include low migration rates of transplanted cells into host retina and an absence of data describing chemotactic signaling guiding migration of transplanted cells in the damaged retinal microenvironment. To elucidate chemotactic signaling guiding transplanted cell migration, bioinformatics modeling of PPC transplantation into light-damaged retina was performed. The bioinformatics modeling analyzed whole-genome expression data and matched PPC chemotactic cell-surface receptors to cognate ligands expressed in the light-damaged retinal microenvironment. A library of significantly predicted chemotactic ligand-receptor pairs, as well as downstream signaling networks was generated. PPC and RPC migration in microfluidic ligand gradients were analyzed using a highly predicted ligand-receptor pair, SDF-1α - CXCR4, and both PPCs and RPCs exhibited significant chemotaxis. This work present a systems level model and begins to elucidate molecular mechanisms involved in PPC and RPC migration within the damaged retinal microenvironment.
Neuropeptide Y-family peptides and receptors in the elephant shark, Callorhinchus milii confirm gene duplications before the gnathostome radiation.
Genomics, 2009

We describe here the repertoire of neuropeptide Y (NPY) peptides and receptors in the elephant shark Callorhinchus milii, belonging to the chondrichthyans that diverged from the rest of the gnathostome (jawed vertebrate) lineage about 450 million years ago and the first chondrichthyan with a genome project. We have identified two peptide genes that are orthologous to NPY and PYY (peptide YY) in other vertebrates, and seven receptor genes orthologous to the Y1, Y2, Y4, Y5, Y6, Y7 and Y8 subtypes found in tetrapods and teleost fishes. The repertoire of peptides and receptors seems to reflect the ancestral configuration in the predecessor of all gnathostomes, whereas other lineages such as mammals and teleosts have lost one or more receptor genes or have acquired 1-2 additional peptide genes. Both the peptides and receptors showed broad and overlapping mRNA expression which may explain why some receptor gene losses could take place in some lineages, but leaves open the question why all the known ancestral receptors have been retained in the elephant shark.
The Zinc Finger Transcription Factor Sp9 Is Required for the Development of Striatopallidal Projection Neurons.
Cell reports, 2016

Striatal medium-sized spiny neurons (MSNs), composed of striatonigral and striatopallidal neurons, are derived from the lateral ganglionic eminence (LGE). We find that the transcription factor Sp9 is expressed in LGE progenitors that generate nearly all striatal MSNs and that Sp9 expression is maintained in postmitotic striatopallidal MSNs. Sp9-null mice lose most striatopallidal MSNs because of decreased proliferation of striatopallidal MSN progenitors and increased Bax-dependent apoptosis, whereas the development of striatonigral neurons is largely unaffected. ChIP qPCR provides evidence that Ascl1 directly binds the Sp9 promoter. RNA-seq and in situ hybridization reveal that Sp9 promotes expression of Adora2a, P2ry1, Gpr6, and Grik3 in the LGE and striatum. Thus, Sp9 is crucial for the generation, differentiation, and survival of striatopallidal MSNs.
Molecular aspects involved in swimming exercise training reducing anhedonia in a rat model of depression.
Neuroscience, 2011

Patients suffering from depression frequently display hyperactivity of the hypothalamic-pituitary-adrenal axis (HPA) resulting in elevated cortisol levels. One main symptom of this condition is anhedonia. There is evidence that exercise training can be used as a rehabilitative intervention in the treatment of depressive disorders. In this scenario, the aim of the present study was to assess the effect of an aerobic exercise training protocol on the depressive-like behavior, anhedonia, induced by repeated dexamethasone administration. The study was carried out on adult male Wistar rats randomly divided into four groups: the "control group" (C), "exercise group" (E), "dexamethasone group" (D) and the "dexamethasone plus exercise group" (DE). The exercise training consisted of swimming (1 h/d, 5 d/wk) for 3 weeks, with an overload of 5% of the rat body weight. Every day rats were injected with either dexamethasone (D/DE) or saline solution (C/E). Proper positive controls, using fluoxetine, were run in parallel. Decreased blood corticosterone levels, reduced adrenal cholesterol synthesis and adrenal weight (HPA disruption), reduced preference for sucrose consumption and increased immobility time (depressive-like behavior), marked hippocampal DNA oxidation, increased IL-10 and total brain-derived neurotrophic factor (BDNF; pro-plus mature-forms) and a severe loss of body mass characterized the dexamethasone-treated animals. Besides increasing testosterone blood concentrations, the swim training protected depressive rats from the anhedonic state, following the same profile as fluoxetine, and also from the dexamethasone-induced impaired neurochemistry. The data indicate that physical exercise could be a useful tool in preventing and treating depressive disorders.
The dual functions of the extreme N-terminus of TDP-43 in regulating its biological activity and inclusion formation.
Human molecular genetics, 2013

TAR DNA-binding protein-43 (TDP-43) is the principal component of ubiquitinated inclusions in amyotrophic lateral sclerosis (ALS) and the most common pathological subtype of frontotemporal dementia-frontotemporal lobar degeneration with TDP-43-positive inclusions (FTLD-TDP). To date, the C-terminus of TDP-43, which is aggregation-prone and contains almost all ALS-associated mutations, has garnered much attention while the functions of the N-terminus of TDP-43 remain largely unknown. To bridge this gap in our knowledge, we utilized novel cell culture and computer-assisted models to evaluate which region(s) of TDP-43 regulate its folding, self-interaction, biological activity and aggregation. We determined that the extreme N-terminus of TDP-43, specifically the first 10 residues, regulates folding of TDP-43 monomers necessary for proper homodimerization and TDP-43-regulated splicing. Despite such beneficial functions, we discovered an interesting dichotomy: full-length TDP-43 aggregation, which is believed to be a pathogenic process, also requires the extreme N-terminus of TDP-43. As such, we provide new insight into the structural basis for TDP-43 function and aggregation, and we suggest that stabilization of TDP-43 homodimers, the physiologically active form of TDP-43, may be a promising therapeutic strategy for ALS and FTLD-TDP.
Lipids in Ca2+ signalling--an introduction.
Cell calcium, 2009

Lipids and lipid-derived metabolites are increasingly recognised as bonafide signalling molecules that regulate many cellular processes. These include the well-established InsP(3), diacylglycerol (DAG), PIP(2), PIP(3) and arachidonic acid (AA), as well as other poly-unsaturated fatty acids (PUFAs), lysophospholipids, sphingolipids, endocannabinoids and endovanilloids. They regulate a plethora of molecules that are involved in Ca(2+) signalling, including various ion channels, pumps and transporters, thereby triggering, modulating and fine-tuning Ca(2+) signals. Although appreciated individually, it seems timely to highlight the overall impact of lipids as signalling molecules and their role in Ca(2+) signalling, and this is the aim of this special issue of Cell Calcium.
Neuropeptide Trefoil Factor 3 Reverses Depressive-Like Behaviors by Activation of BDNF-ERK-CREB Signaling in Olfactory Bulbectomized Rats.
International journal of molecular sciences, 2015

The trefoil factors (TFFs) are a family of three polypeptides, among which TFF1 and TFF3 are widely distributed in the central nervous system. Our previous study indicated that TFF3 was a potential rapid-onset antidepressant as it reversed the depressive-like behaviors induced by acute or chronic mild stress. In order to further identify the antidepressant-like effect of TFF3, we applied an olfactory bulbectomy (OB), a classic animal model of depression, in the present study. To elucidate the mechanism underlying the antidepressant-like activity of TFF3, we tested the role of brain-derived neurotrophic factor (BDNF)-extracellular signal-related kinase (ERK)-cyclic adenosine monophosphate response element binding protein (CREB) signaling in the hippocampus in the process. Chronic systemic administration of TFF3 (0.1 mg/kg, i.p.) for seven days not only produced a significant antidepressant-like efficacy in the OB paradigm, but also restored the expression of BDNF, pERK, and pCREB in the hippocampal CA3. Inhibition of BDNF or extracellular signal-related kinase (ERK) signaling in CA3 blocked the antidepressant-like activity of TFF3 in OB rats. Our findings further confirmed the therapeutic effect of TFF3 against depression and suggested that the normalization of the BDNF-ERK-CREB pathway was involved in the behavioral response of TFF3 for the treatment of depression.
Data-driven models in human neuroscience and neuroengineering.
Current opinion in neurobiology, 2019

Discoveries in modern human neuroscience are increasingly driven by quantitative understanding of complex data. Data-intensive approaches to modeling have promise to dramatically advance our understanding of the brain and critically enable neuroengineering capabilities. In this review, we provide an accessible primer to modern modeling approaches and highlight recent data-driven discoveries in the domains of neuroimaging, single-neuron and neuronal population responses, and device neuroengineering. Further, we suggest that meaningful progress requires the community to tackle open challenges in the realms of model interpretability and generalizability, training pipelines of data-fluent human neuroscientists, and integrated consideration of data ethics.
Metabolomics Study of the Synergistic Killing of Polymyxin B in Combination with Amikacin against Polymyxin-Susceptible and -Resistant Pseudomonas aeruginosa.
Antimicrobial agents and chemotherapy, 2019

In the present study, we employed untargeted metabolomics to investigate the synergistic killing mechanism of polymyxin B in combination with an aminoglycoside, amikacin, against a polymyxin-susceptible isolate of
Specificity of speech motor learning.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2008

The idea that the brain controls movement using a neural representation of limb dynamics has been a dominant hypothesis in motor control research for well over a decade. Speech movements offer an unusual opportunity to test this proposal by means of an examination of transfer of learning between utterances that are to varying degrees matched on kinematics. If speech learning results in a generalizable dynamics representation, then, at the least, learning should transfer when similar movements are embedded in phonetically distinct utterances. We tested this idea using three different pairs of training and transfer utterances that substantially overlap kinematically. We find that, with these stimuli, speech learning is highly contextually sensitive and fails to transfer even to utterances that involve very similar movements. Speech learning appears to be extremely local, and the specificity of learning is incompatible with the idea that speech control involves a generalized dynamics representation.
Chronic Stress Prevents Cortico-Accumbens Cue Encoding and Alters Conditioned Approach.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2021

Chronic stress impairs the function of multiple brain regions and causes severe hedonic and motivational deficits. One brain region known to be susceptible to these effects is the PFC. Neurons in this region, specifically neuronal projections from the prelimbic region (PL) to the nucleus accumbens core (NAcC), have a significant role in promoting motivated approach. However, little is known about how activity in this pathway changes during associative learning to encode cues that promote approach. Less is known about how activity in this pathway may be altered by stress. In this study, an intersectional fiber photometry approach was used in male Sprague Dawley rats engaged in a Pavlovian autoshaping design to characterize the involvement of the PL-NAcC pathway in the typical acquisition of learned approach (directed at both the predictive cue and the goal), and its potential alteration by stress. Specifically, the hypothesis that neural activity in PL-NAcC would encode a Pavlovian approach cue and that prior exposure to chronic stress would disrupt both the nature of conditioned approach and the encoding of a cue that promotes approach was tested. Results of the study demonstrated that the rapid acquisition of conditioned approach was associated with cue-induced PL-NAcC activity. Prior stress both reduced cue-directed behavior and impaired the associated cortical activity. These findings demonstrate that prior stress diminishes the task-related activity of a brain pathway that regulates approach behavior. In addition, the results support the interpretation that stress disrupts reward processing by altering the incentive value of associated cues.
Let's make microglia great again in neurodegenerative disorders.
Journal of neural transmission (Vienna, Austria : 1996), 2018

All of the common neurodegenerative disorders-Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and prion diseases-are characterized by accumulation of misfolded proteins that trigger activation of microglia; brain-resident mononuclear phagocytes. This chronic form of neuroinflammation is earmarked by increased release of myriad cytokines and chemokines in patient brains and biofluids. Microglial phagocytosis is compromised early in the disease process, obfuscating clearance of abnormal proteins. This review identifies immune pathologies shared by the major neurodegenerative disorders. The overarching concept is that aberrant innate immune pathways can be targeted for return to homeostasis in hopes of coaxing microglia into clearing neurotoxic misfolded proteins.