rudyvdbrink/CitationDatabase huggingface dataset:
Extensive genetics of ALS: a population-based study in Italy.
Neurology, 2012

To assess the frequency and clinical characteristics of patients with mutations of major amyotrophic lateral sclerosis (ALS) genes in a prospectively ascertained, population-based epidemiologic series of cases.
Topical application of Photofrin
Journal of plastic, reconstructive & aesthetic surgery : JPRAS, 2018

The prognosis of patients suffering from malignant cutaneous neoplasms can be improved by early diagnosis. Exact demarcation of tumor margins could contribute to optimum results in surgical excision and reconstruction. The purpose of our study is to evaluate Photofrin
Estrogen and the aging brain: an elixir for the weary cortical network.
Annals of the New York Academy of Sciences, 2010

The surprising discovery in 1990 that estrogen modulates hippocampal structural plasticity launched a whole new field of scientific inquiry. Over the past two decades, estrogen-induced spinogenesis has been described in several brain areas involved in cognition in a number of species, in both sexes and on multiple time scales. Exploration into the interaction between estrogen and aging has illuminated some of the hormone's neuroprotective effects, most notably on age-related cognitive decline in nonhuman primates. Although there is still much to be learned about the mechanisms by which estrogen exerts its actions, key components of the signal transduction pathways are beginning to be elucidated and nongenomic actions via membrane bound estrogen receptors are of particular interest. Future studies are focused on identifying the most clinically relevant hormone treatment, as well as the potential identification of new therapeutics that can prevent or reverse age-related cognitive impairment by intercepting specific signal transduction pathways initiated by estrogen.
Age-related changes in Egr1 transcription and DNA methylation within the hippocampus.
Hippocampus, 2016

Aged animals show functional alterations in hippocampal neurons that lead to deficits in synaptic plasticity and changes in cognitive function. Transcription of immediate-early genes (IEGs), including Egr1, is necessary for processes such as long-term potentiation and memory consolidation. Here, we show an age-related reduction in the transcription of Egr1 in the dentate gyrus following spatial behavior, whereas in the area CA1, Egr1 is reduced at rest, but its transcription can be effectively driven by spatial behavior to levels equivalent to those observed in adult animals. One mechanism possibly contributing to these aging-related changes is an age-associated, CpG site-specific change in methylation in DNA associated with the promoter region of the Egr1 gene. Our results add to a growing body of work demonstrating that complex transcriptional and epigenetic changes in the hippocampus significantly contribute to brain and cognitive aging. © 2016 Wiley Periodicals, Inc.
Attitudes of Asian Parkinson patients towards brain donation.
Cell and tissue banking, 2019

Histopathological examination of brain tissue is required for better understanding of neurodegenerative conditions such as Parkinson's disease and related disorders. However, patient willingness remains the greatest hurdle hampering participation in brain donation for research. While there is extensive research being conducted on the subject in West, to the best of our knowledge, there are no studies done in this regard in Asia. This cross-sectional survey was conducted on 105 Parkinson's disease patients to assess their knowledge, beliefs and attitude towards brain donation in an Asian population. The majority of the participants (78%) acknowledged the importance of donation of brain for research, and 70% believed that their donated brain samples would be handled professionally. Fifty percent participants were willing to consider donating their brain for research. Motivating factors for brain donation included altruism (87%) and contribution to advance medical knowledge (80%). Common reasons for unwillingness towards brain donation were stress for family (30%), disfigurement of body (25%), and having a conservative mindset (23%). About one-third of the participants preferred to be approached for brain donation after their first clinic visit. Most patients preferred either their treating neurologists (66%) or research staff (18%) to discuss brain donation with. Participation for brain donation may be increased further with greater patient and public education to overcome misconceptions and change mindsets.
Acute treatment with valproic acid and l-thyroxine ameliorates clinical signs of experimental autoimmune encephalomyelitis and prevents brain pathology in DA rats.
Neurobiology of disease, 2014

Multiple sclerosis (MS) is the most common chronic inflammatory demyelinating disease of the central nervous system (CNS) in young adults. Chronic treatments with histone deacetylase inhibitors (HDACis) have been reported to ameliorate experimental autoimmune encephalomyelitis (EAE), a rodent model of MS, by targeting immune responses. We have recently shown that the HDAC inhibition/knockdown in the presence of thyroid hormone (T3) can also promote oligodendrocyte (OL) differentiation and expression of myelin genes in neural stem cells (NSCs) and oligodendrocyte precursors (OPCs). In this study, we found that treatment with an HDACi, valproic acid (VPA), and T3, alone or in combination, directly affects encephalitogenic CD4+ T cells. VPA, but not T3, compromised their proliferation, while both molecules reduced the frequency of IL-17-producing cells. Transfer of T3, VPA and VPA/T3 treated encephalitogenic CD4+ T cells into naïve rats induced less severe EAE, indicating that the effects of these molecules are persistent and do not require their maintenance after the initial stimuli. Thus, we investigated the effect of acute treatment with VPA and l-thyroxine (T4), a precursor of T3, on myelin oligodendrocyte glycoprotein-induced EAE in Dark Agouti rats, a close mimic of MS. We found that a brief treatment after disease onset led to sustained amelioration of EAE and prevention of inflammatory demyelination in the CNS accompanied with a higher expression of myelin-related genes in the brain. Furthermore, the treatment modulated immune responses, reduced the number of CD4+ T cells and affected the Th1 differentiation program in the brain. Our data indicate that an acute treatment with VPA and T4 after the onset of EAE can produce persistent clinically relevant therapeutic effects by limiting the pathogenic immune reactions while promoting myelin gene expression.
Sequential generation of two distinct synapse-driven network patterns in developing neocortex.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2008

Developing cortical networks generate a variety of coherent activity patterns that participate in circuit refinement. Early network oscillations (ENOs) are the dominant network pattern in the rodent neocortex for a short period after birth. These large-scale calcium waves were shown to be largely driven by glutamatergic synapses albeit GABA is a major excitatory neurotransmitter in the cortex at such early stages, mediating synapse-driven giant depolarizing potentials (GDPs) in the hippocampus. Using functional multineuron calcium imaging together with single-cell and field potential recordings to clarify distinct network dynamics in rat cortical slices, we now report that the developing somatosensory cortex generates first ENOs then GDPs, both patterns coexisting for a restricted time period. These patterns markedly differ by their developmental profile, dynamics, and mechanisms: ENOs are generated before cortical GDPs (cGDPs) by the activation of glutamatergic synapses mostly through NMDARs; cENOs are low-frequency oscillations (approximately 0.01 Hz) displaying slow kinetics and gradually involving the entire network. At the end of the first postnatal week, GABA-driven cortical GDPs can be reliably monitored; cGDPs are recurrent oscillations (approximately 0.1 Hz) that repetitively synchronize localized neuronal assemblies. Contrary to cGDPs, cENOs were unexpectedly facilitated by short anoxic conditions suggesting a contribution of glutamate accumulation to their generation. In keeping with this, alterations of extracellular glutamate levels significantly affected cENOs, which are blocked by an enzymatic glutamate scavenger. Moreover, we show that a tonic glutamate current contributes to the neuronal membrane excitability when cENOs dominate network patterns. Therefore, cENOs and cGDPs are two separate aspects of neocortical network maturation that may be differentially engaged in physiological and pathological processes.
Explaining left lateralization for words in the ventral occipitotemporal cortex.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011

Reading is a uniquely human task and therefore any sign of neuronal activation that is specific to reading is of considerable interest. One intriguing observation is that ventral occipitotemporal (vOT) activation is more strongly left lateralized for written words than other visual stimuli. This has contributed to claims that left vOT plays a special role in reading. Here, we investigated whether left lateralized vOT responses for words were the consequence of visual feature processing, visual word form selectivity, or higher level language processing. Using fMRI in 82 skilled readers, our paradigm compared activation and lateralization for words and nonlinguistic stimuli during different tasks. We found that increased left lateralization for words relative to pictures was the consequence of reduced activation in right vOT rather than increased activation in left vOT. We also found that the determinants of lateralization varied with the subregion of vOT tested. In posterior vOT, lateralization depended on the spatial frequency of the visual inputs. In anterior vOT, lateralization depended on the semantic demands of the task. In middle vOT, lateralization depended on a combination of visual expertise in the right hemisphere and semantics in the left hemisphere. These results have implications for interpreting left lateralized vOT activation during reading. Specifically, left lateralized activation in vOT does not necessarily indicate an increase in left vOT processing but is instead a consequence of decreased right vOT function. Moreover, the determinants of lateralization include both visual and semantic factors depending on the subregion tested.
Substructural hippocampal glucose metabolism observed on PET/MRI.
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2010

The hippocampus is one of the best-known neural structures in the brain and has been of interest in observing the substructures and their metabolic functions. However, it has been difficult to distinguish its substructures and functions in vivo because of its small size.
The Mouse Gambling Task: Assessing Individual Decision-making Strategies in Mice.
Bio-protocol, 2020

Decision-making is a complex cognitive process which consists of choosing one option among several alternatives. In humans, this process is featured in the Iowa gambling task (IGT), a decision-making task that mimics real life situations by reproducing uncertain conditions based on probabilistic rewards or penalties (see Background). Several authors wanted to adapt the IGT in rodents with subtle differences in protocols that match various aspects of the human task. Here we propose, for the first time in mice, a protocol that contains the most important characteristics of the IGT: 4 different options, choices based on 4 ambiguous outcomes with immediate and long term rewards, a total of 100 trials, no learning of the contingency before the task, and presence of both a certain reward and a probable penalty. During this task, mice have to choose between options more or less advantageous in the short and long term by developing a decision-making strategy that differs between individuals. Therefore, the strength of this protocol is that it is one of the first to enable the study of decision-making in a complex situation, and demonstrates inter-individual differences regarding decision-making strategies in mice.
No evidence for cerebellar abnormality in adults with developmental dyslexia.
Experimental brain research, 2018

Developmental dyslexia is commonly believed to result from a deficiency in the recognition and processing of speech sounds. According to the cerebellar deficit hypothesis, this phonological deficit is caused by deficient cerebellar function. In the current study, 26 adults with developmental dyslexia and 25 non-dyslexic participants underwent testing of reading-related skills, cerebellar functions, and MRI scanning of the brain. Anatomical assessment of the cerebellum was conducted with voxel-based morphometry. Behavioural evidence, that was indicative of impaired cerebellar function, was found to co-occur with reading impairments in the dyslexic subjects, but a causal relation between the two was not observed. No differences in local grey matter volume, nor in structure-function relationships within the cerebellum were found between the two groups. Possibly, the observed behavioural pattern is due to aberrant white matter connectivity. In conclusion, no support for the cerebellar deficit hypothesis or the presence of anatomical differences of the cerebellum in adults with developmental dyslexia was found.
Morphine preconditioning reduces lipopolysaccharide and interferon-gamma-induced mouse microglial cell injury via delta 1 opioid receptor activation.
Neuroscience, 2010

Microglial cells play an important role in the inflammatory response of a broad range of brain diseases including stroke, brain infection and neurodegenerative diseases. However, there is very little information regarding how to protect microglial cells. Here, we showed that incubation of the C8-B4 mouse microglial cells with lipopolysaccharide (LPS) plus interferon-gamma (IFN gamma) induced cytotoxicity as assessed by the amount of lactate dehydrogenase (LDH) released from the cells. Preconditioning the cells with morphine for 30 min concentration-dependently reduced LPS plus IFN gamma-induced cell injury. This morphine preconditioning effect was abolished by naloxone, a general opioid receptor antagonist, by naltrindole, a selective delta opioid receptor antagonist and by 7-benzylidenenaltrexone maleate, a selective delta(1) opioid receptor antagonist. However, this protective effect was not affected by beta-funaltrexamine, a selective mu opioid receptor antagonist, nor-binaltorphimine, a selective kappa opioid receptor antagonist or naltriben, a selective delta(2) opioid receptor antagonist. LPS plus IFN gamma induced the expression of inducible nitric oxide synthase (iNOS), which was not affected by morphine preconditioning. Our results suggest that morphine induced a preconditioning effect in microglial cells. This effect may be mediated by delta 1 opioid receptors and may not be through inhibiting the expression of iNOS, a potentially harmful protein.
Essential role for phosphatidylinositol 4,5-bisphosphate in the expression, regulation, and gating of the slow afterhyperpolarization current in the cerebral cortex.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011

Many neurons of the CNS and peripheral nervous system express a slow afterhyperpolarization that is mediated by a slow calcium-activated potassium current. Previous work has shown that this aftercurrent regulates repetitive firing and is an important target for neuromodulators signaling through receptors coupled to G-proteins of the Gα(q-11) and Gα(s) subtypes. Yet, despite considerable effort, a molecular-level understanding of the potassium current underlying the slow afterhyperpolarization and its modulation has proven elusive. Here, we use a combination of pharmacological and molecular biological approaches in cortical brain slices to show that the functional expression of the slow calcium-activated afterhyperpolarizing current in pyramidal cells is critically dependent on membrane phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P(2)] and that this dependence accounts for its inhibition by 5-HT(2A) receptors. Furthermore, we show that PtdIns(4,5)P(2) regulates the calcium sensitivity of I(sAHP) in a manner that suggests it acts downstream from the rise in intracellular calcium. These results clarify key functional aspects of the slow afterhyperpolarization current and its modulation by 5-HT(2A) receptors and point to a key role for PtdIns(4,5)P(2) in the gating of this current.
Improving the Delivery of Levodopa in Parkinson's Disease: A Review of Approved and Emerging Therapies.
CNS drugs, 2020

Levodopa is the most effective drug for the treatment of Parkinson's disease, but its use as an oral medication is complicated by its erratic absorption, extensive metabolism and short plasma half-life. On long-term use and with disease progression, there is a high incidence of motor and non-motor complications, which remain a major clinical and research challenge. It is widely accepted that levodopa needs to be administered using formulations that result in good and consistent bioavailability and the physiologically relevant and continuous formation of dopamine in the brain to maximise its efficacy while avoiding and reversing 'wearing off' and dyskinesia. However, the physicochemical properties of levodopa along with its pharmacokinetic and pharmacodynamic profile make it difficult to deliver the drug in a manner that fulfils these criteria. In this review, we examine the problems associated with the administration of levodopa in Parkinson's disease and how the use of novel technologies and delivery devices is leading to a more consistent and sustained levodopa delivery with the aim of controlling motor function as well as non-motor symptoms.
Serum protein changes in a rat model of chronic pain show a correlation between animal and humans.
Scientific reports, 2017

In previous works we showed the overexpression of some proteins in biological fluids from patients suffering chronic pain. In this proteomic study we analysed serum from a rat model of neuropathic pain obtained by the chronic constriction injury (CCI) of sciatic nerve, at two time intervals, 2 and 5 weeks after the insult, to find proteins involved in the expression or mediation of pain. Sham-operated and CCI rats were treated with saline or indomethacin. Two weeks after ligation, we identified three serum proteins overexpressed in CCI rats, two of which, alpha-1-macroglobulin and vitamin D-binding protein (VDBP), remained increased 5 weeks post-surgery; at this time interval, we found increased levels of further proteins, namely apolipoprotein A-I (APOA1), apolipoprotein E (APOE), prostaglandin-H2 D-isomerase (PTGDS) and transthyretin (TTR), that overlap the overexpressed proteins found in humans. Indomethacin treatment reversed the effects of ligation. The qPCR analysis showed that transcript levels of APOA1, APOE, PTGDS and VDBP were overexpressed in the lumbar spinal cord (origin of sciatic nerve), but not in the striatum (an unrelated brain region), of CCI rats treated with saline 5 weeks after surgery, demonstrating that the lumbar spinal cord is a possible source of these proteins.
Social reward: interactions with social status, social communication, aggression, and associated neural activation in the ventral tegmental area.
The European journal of neuroscience, 2013

Nearly all species engage in a variety of intraspecific social interactions, and there is evidence that these interactions are rewarding. Less is known, however, about the factors that influence social reward. Using the conditioned place preference paradigm, we tested whether social interactions are rewarding for male Syrian hamsters. We also tested whether social stimuli increase neural activation in the ventral tegmental area (VTA), a component of the mesolimbic reward system, and how individual differences in social behavior and experience influence neural activation. In the present study, we found that hamsters developed a conditioned place preference for social interactions, but the effects were significantly stronger in dominant animals compared with subordinates. The number of Fos-immunoreactive cells in the VTA was significantly higher in hamsters that had engaged in a direct social encounter compared with hamsters exposed to a caged stimulus hamster or controls. Interestingly, socially experienced males had more Fos-immunoreactive cells in the VTA than socially naive males after exposure to a social stimulus. Surprisingly, the amount of Fos immunoreactivity in the VTA induced by a social stimulus was correlated with the amount of aggressive/dominance behaviors that had been observed during interactions that had occurred 2 months earlier. Our results indicate that social interactions between males are rewarding, and that social dominance increases the reward value. Social interactions stimulate the mesolimbic reward system, and social experience enhances its response to novel social stimuli and may produce long-term changes in the neural mechanisms that mediate the maintenance of dominance over long periods of time.
A linear model for event-related respiration responses.
Journal of neuroscience methods, 2016

Cognitive processes influence respiratory physiology. This may allow inferring cognitive states from measured respiration. Here, we take a first step towards this goal and investigate whether event-related respiratory responses can be identified, and whether they are accessible to a model-based approach.
Combined fused in sarcoma-positive (FUS+) basophilic inclusion body disease and atypical tauopathy presenting with an amyotrophic lateral sclerosis/motor neurone disease (ALS/MND)-plus phenotype.
Neuropathology and applied neurobiology, 2019

Amyotrophic lateral sclerosis/motor neurone disease (ALS/MND) is characterized by the presence of inclusions containing TDP-43 within motor neurones. In rare cases, ALS/MND may be associated with inclusions containing other proteins, such as fused in sarcoma (FUS), while motor system pathology may rarely be a feature of other neurodegenerative disorders. We here have investigated the association of FUS and tau pathology.
The initial impact of the SARS-CoV-2 pandemic on epilepsy research.
Epilepsia open, 2021

The COVID-19 pandemic has changed the face of many practices throughout the world. Through necessity to minimize spread and provide clinical care to those with severe disease, focus has been on limiting face-to-face contact. Research in many areas has been put on hold. We sought to determine the impact of the COVID-19 pandemic on epilepsy research from international basic science and clinical researchers. Responses to five questions were solicited through a convenience sample by direct email and through postings on the ILAE social media accounts and an ILAE online platform (utilizing Slack). Information was collected from 15 respondents in 11 countries by email or via Zoom interviews between May 19, 2020, and June 4, 2020. Several themes emerged including a move to virtual working, project delays with laboratory work halted and clinical work reduced, funding concerns, a worry about false data with regard to COVID research and concern about research time lost. However, a number of positive outcomes were highlighted, not least the efficiency of online working and other adaptations that could be sustained in the future.