rudyvdbrink/CitationDatabase huggingface dataset:
Midazolam inhibits hippocampal long-term potentiation and learning through dual central and peripheral benzodiazepine receptor activation and neurosteroidogenesis.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010

Benzodiazepines (BDZs) enhance GABA(A) receptor inhibition by direct actions on central BDZ receptors (CBRs). Although some BDZs also bind mitochondrial receptors [translocator protein (18 kDa) (TSPO)] and promote the synthesis of GABA-enhancing neurosteroids, the role of neurosteroids in the clinical effects of BDZs is unknown. In rat hippocampal slices, we compared midazolam, an anesthetic BDZ, with clonazepam, an anticonvulsant/anxiolytic BDZ that activates CBRs selectively. Midazolam, but not clonazepam, increased neurosteroid levels in CA1 pyramidal neurons without changing TSPO immunostaining. Midazolam, but not clonazepam, also augmented a form of spike inhibition after stimulation adjacent to the pyramidal cell layer and inhibited induction of long-term potentiation. These effects were prevented by finasteride, an inhibitor of neurosteroid synthesis, or 17PA [17-phenyl-(3α,5α)-androst-16-en-3-ol], a blocker of neurosteroid effects on GABA(A) receptors. Moreover, the synaptic effects were mimicked by a combination of clonazepam with FGIN (2-[2-(4-fluorophenyl)-1H-indol-3-yl]-N,N-dihexylacetamide), a selective TSPO agonist, or a combination of clonazepam with exogenous allopregnanolone. Consistent with these in vitro results, finasteride abolished the effects of midazolam on contextual fear learning when administrated 1 d before midazolam injection. Thus, dual activation of CBRs and TSPO appears to result in unique actions of clinically important BDZs. Furthermore, endogenous neurosteroids are shown to be important regulators of pyramidal neuron function and synaptic plasticity.
Integration of H-2Z1, a somatosensory cortex-expressed transgene, interferes with the expression of the Satb1 and Tbc1d5 flanking genes and affects the differentiation of a subset of cortical interneurons.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012

H-2Z1 is an enhancer trap transgenic mouse line in which the lacZ reporter delineates the somatosensory area of the cerebral cortex where it is expressed in a subset of layer IV neurons. In the search of somatosensory specific genes or regulatory sequences, we mapped the H-2Z1 transgene insertion site to chromosome 17, 100 and 460 kb away from Tbc1d5 and Satb1 flanking genes. We show here that insertion of the H-2Z1 transgene results in three distinct outcomes. First, a genetic background-sensitive expression of lacZ in several brain and body structures. While four genes in a 1 Mb region around the insertion are expressed in the barrel cortex, H-2Z1 expression resembles more that of its two direct neighbors. Moreover, H-2Z1 closely reports most of the body and brain expression sites of the Satb1 chromatin remodeling gene including tooth buds, thymic epithelium, pontine nuclei, fastigial cerebellar nuclei, and cerebral cortex. Second, the H-2Z1 transgene causes insertional mutagenesis of Tbc1d5 and Satb1, leading to a strong decrease in their expressions. Finally, insertion of H-2Z1 affects the differentiation of a subset of cortical GABAergic interneurons, a possible consequence of downregulation of Satb1 expression. Thus, the H-2Z1 "somatosensory" transgene is inserted in the regulatory landscape of two genes highly expressed in the developing somatosensory cortex and reports for a subdomain of their expression profiles. Together, our data suggest that regulation of H-2Z1 expression results from local and remote genetic interactions.
An integrated view of empathy: psychology, philosophy, and neuroscience.
Integrative psychological & behavioral science, 2009

In this paper, we will examine and untangle a conflict mainly between a developmental psychologist, Martin Hoffman and a social psychologist, Daniel Batson. According to Hoffman, empathic distress, a vicarious feeling through empathy, is transformed into an altruistic motivation. Batson and others on the other hand, criticize Hoffman, claiming that empathic altruism has no relation with empathic distress. We will point out some problems with Batson's position by referring to the results of fMRI experiments that suggest empathic distress and empathic altruism share a common basis, and defend Hoffman's argument. This will also offer new insights into the evolution of empathy.
NCAM regulates temporal specification of neural progenitor cells via profilin2 during corticogenesis.
The Journal of cell biology, 2020

The development of cerebral cortex requires spatially and temporally orchestrated proliferation, migration, and differentiation of neural progenitor cells (NPCs). The molecular mechanisms underlying cortical development are, however, not fully understood. The neural cell adhesion molecule (NCAM) has been suggested to play a role in corticogenesis. Here we show that NCAM is dynamically expressed in the developing cortex. NCAM expression in NPCs is highest in the neurogenic period and declines during the gliogenic period. In mice bearing an NPC-specific NCAM deletion, proliferation of NPCs is reduced, and production of cortical neurons is delayed, while formation of cortical glia is advanced. Mechanistically, NCAM enhances actin polymerization in NPCs by interacting with actin-associated protein profilin2. NCAM-dependent regulation of NPCs is blocked by mutations in the profilin2 binding site. Thus, NCAM plays an essential role in NPC proliferation and fate decision during cortical development by regulating profilin2-dependent actin polymerization.
Glial reactivity in resistance to methamphetamine-induced neurotoxicity.
Journal of neurochemistry, 2013

Neurotoxic regimens of methamphetamine (METH) result in reactive microglia and astrocytes in striatum. Prior data indicate that rats with partial dopamine (DA) loss resulting from prior exposure to METH are resistant to further decreases in striatal DA when re-exposed to METH 30 days later. Such resistant animals also do not show an activated microglia phenotype, suggesting a relation between microglial activation and METH-induced neurotoxicity. To date, the astrocyte response in such resistance has not been examined. Thus, this study examined glial-fibrillary acidic protein (GFAP) and CD11b protein expression in striata of animals administered saline or a neurotoxic regimen of METH on post-natal days 60 and/or 90 (Saline:Saline, Saline:METH, METH:Saline, METH:METH). Consistent with previous work, animals experiencing acute toxicity (Saline:METH) showed both activated microglia and astocytes, whereas those resistant to the acute toxicity (METH:METH) did not show activated microglia. Interestingly, GFAP expression remained elevated in rats exposed to METH at PND60 (METH:Saline), and was not elevated further in resistant rats treated for the second time with METH (METH:METH). These data suggest that astrocytes remain reactive up to 30 days post-METH exposure. In addition, these data indicate that astrocyte reactivity does not reflect acute, METH-induced DA terminal toxicity, whereas microglial reactivity does.
Photo-Induced Oxidative Stress Impairs Mitochondrial Metabolism in Neurons and Astrocytes.
Molecular neurobiology, 2018

Photodynamic therapy is selective destruction of cells stained with a photosensitizer upon irradiation with light at a specific wavelength in the presence of oxygen. Cell death upon photodynamic treatment is known to occur mainly due to free radical production and subsequent development of oxidative stress. During photodynamic therapy of brain tumors, healthy cells are also damaged; considering this, it is important to investigate the effect of the treatment on normal neurons and glia. We employed live-cell imaging technique to investigate the cellular mechanism of photodynamic action of radachlorin (200 nM) on neurons and astrocytes in primary rat cell culture. We found that the photodynamic effect of radachlorin increases production of reactive oxygen species measured by dihydroethidium and significantly decrease mitochondrial membrane potential. Mitochondrial depolarization was independent of opening of mitochondrial permeability transition pore and was insensitive to blocker of this pore cyclosporine A. However, irradiation of cells with radachlorin dramatically decreased NADH autofluorescence and also reduced mitochondrial NADH pool suggesting inhibition of mitochondrial respiration by limitation of substrate. This effect could be prevented by inhibition of poly (ADP-ribose) polymerase (PARP) with DPQ. Thus, irradiation of neurons and astrocytes in the presence of radachlorin leads to activation of PARP and decrease in NADH that leads to mitochondrial dysfunction.
Rhythmic entrainment as a musical affect induction mechanism.
Neuropsychologia, 2017

One especially important feature of metrical music is that it contains periodicities that listeners' bodily rhythms can adapt to. Recent psychological frameworks have introduced the notion of rhythmic entrainment, among other mechanisms, as an emotion induction principle. In this review paper, we discuss rhythmic entrainment as an affect induction mechanism by differentiating four levels of entrainment in humans-perceptual, autonomic physiological, motor, and social-all of which could contribute to a subjective feeling component. We review the theoretical and empirical literature on rhythmic entrainment to music that supports the existence of these different levels of entrainment by describing the phenomena and characterizing the associated underlying brain processes. The goal of this review is to present the theoretical implications and empirical findings about rhythmic entrainment as an important principle at the basis of affect induction via music, since it rests upon the temporal dimension of music, which is a specificity of music as an affective stimulus.
Group cognitive-behavioral therapy for patients with epilepsy and comorbid depression and anxiety.
Epilepsy & behavior : E&B, 2011

Clinical Practice Guidelines for depression and anxiety recommend cognitive-behavioral therapy (CBT) as an equivalent and sometimes more effective treatment than medication. The limited research investigating CBT for anxiety and depression in epilepsy demonstrates mixed results. Described here is a pilot project using an existing group CBT intervention for symptoms of depression and/or anxiety, CBT Basics II, in patients with epilepsy. Eighteen patients with epilepsy, referred by neurologists to address depression and/or anxiety symptoms, completed the 10-week group. Results demonstrated improvements in depression, anxiety, negative automatic thoughts, and cognitive therapy knowledge and skills. The group was generally acceptable to patients as indicated by good attendance rates and only one dropout. This pilot project demonstrates that group CBT is a feasible, acceptable, and promising intervention for patients with epilepsy and comorbid depression and anxiety symptoms.
Analysis of copy number variations at 15 schizophrenia-associated loci.
The British journal of psychiatry : the journal of mental science, 2014

A number of copy number variants (CNVs) have been suggested as susceptibility factors for schizophrenia. For some of these the data remain equivocal, and the frequency in individuals with schizophrenia is uncertain.
Dissociable regulation of instrumental action within mouse prefrontal cortex.
The European journal of neuroscience, 2010

Evaluation of the behavioral 'costs', such as effort expenditure relative to the benefits of obtaining reward, is a major determinant of goal-directed action. Neuroimaging evidence suggests that the human medial orbitofrontal cortex (mOFC) is involved in this calculation and thereby guides goal-directed and choice behavior, but this region's functional significance in rodents is unknown despite extensive work characterizing the role of the lateral OFC in cue-related response inhibition processes. We first tested mice with mOFC lesions in an instrumental reversal task lacking discrete cues signaling reinforcement; here, animals were required to shift responding based on the location of the reinforced aperture within the chamber. Mice with mOFC lesions acquired the reversal but failed to inhibit responding on the previously reinforced aperture, while mice with prelimbic prefrontal cortex lesions were unaffected. When tested on a progressive ratio schedule of reinforcement, mice with prelimbic cortical lesions were unable to maintain responding, resulting in declining response levels. Mice with mOFC lesions, by contrast, escalated responding. Neither lesion affected sensitivity to satiety-specific outcome devaluation or non-reinforcement (i.e. extinction), and neither had effects when placed after animals were trained on a progressive ratio response schedule. Lesions of the ventral hippocampus, which projects to the mOFC, resulted in similar response patterns, while lateral OFC and dorsal hippocampus lesions resulted in response acquisition, though not inhibition, deficits in an instrumental reversal. Our findings thus selectively implicate the rodent mOFC in braking reinforced goal-directed action when reinforcement requires the acquisition of novel response contingencies.
Sleep problems in bipolar disorders: more than just insomnia.
Acta psychiatrica Scandinavica, 2016

Sleep problems in bipolar disorder (BD) are common, but reported rates vary from 10% to 80%, depending on definitions, methodologies and management of potential confounding factors. This multicenter study seeks to address these issues and also compares BD cases with Hypersomnia as well as the more commonly investigated Insomnia and No Sleep Problem groups.
Circadian insights into the biology of depression: Symptoms, treatments and animal models.
Behavioural brain research, 2019

In depression, symptoms range from loss of motivation and energy to suicidal thoughts. Moreover, in depression alterations might be also observed in the sleep-wake cycle and in the daily rhythms of hormonal (e.g., cortisol, melatonin) secretion. Both, the sleep-wake cycle and hormonal rhythms, are regulated by the internal biological clock within the hypothalamic suprachiasmatic nucleus (SCN). Therefore, a dysregulation of the internal mechanism of the SCN might lead in the disturbance of temporal physiology and depression. Hence, circadian symptoms in mood disorders can be used as important biomarkers for the prevention and treatment of depression. Disruptions of daily rhythms in physiology and behavior are also observed in animal models of depression, giving thus an important tool of research for the understanding of the circadian mechanisms implicated in mood disorders. This review discusses the alterations of daily rhythms in depression, and how circadian perturbations might lead in mood changes and depressive-like behavior in humans and rodents respectively. The use of animal models with circadian disturbances and depressive-like behaviors will help to understand the central timing mechanisms underlying depression, and how treating the biological clock(s) it may be possible to improve mood.
Guidelines for animal exercise and training protocols for cardiovascular studies.
American journal of physiology. Heart and circulatory physiology, 2020

Whole body exercise tolerance is the consummate example of integrative physiological function among the metabolic, neuromuscular, cardiovascular, and respiratory systems. Depending on the animal selected, the energetic demands and flux through the oxygen transport system can increase two orders of magnitude from rest to maximal exercise. Thus, animal models in health and disease present the scientist with flexible, powerful, and, in some instances, purpose-built tools to explore the mechanistic bases for physiological function and help unveil the causes for pathological or age-related exercise intolerance. Elegant experimental designs and analyses of kinetic parameters and steady-state responses permit acute and chronic exercise paradigms to identify therapeutic targets for drug development in disease and also present the opportunity to test the efficacy of pharmacological and behavioral countermeasures during aging, for example. However, for this promise to be fully realized, the correct or optimal animal model must be selected in conjunction with reproducible tests of physiological function (e.g., exercise capacity and maximal oxygen uptake) that can be compared equitably across laboratories, clinics, and other proving grounds. Rigorously controlled animal exercise and training studies constitute the foundation of translational research. This review presents the most commonly selected animal models with guidelines for their use and obtaining reproducible results and, crucially, translates state-of-the-art techniques and procedures developed on humans to those animal models.
Gastrointestinal Parasitism in Miranda Donkeys: Epidemiology and Selective Control of Strongyles Infection in the Northeast of Portugal.
Animals : an open access journal from MDPI, 2021

In Portugal, equine parasitism in pasture animals is characterized by high parasitic burden and high helminthic biodiversity; both factors are potentially pathogenic for their hosts. The decrease in the number of donkeys over the last years in Portugal, their importance in rural lowland and mountain ecosystems and pastures and the scarce information regarding their parasitism led to this research, which aimed to evaluate the parasitological status of a Miranda donkey breed population, a native breed mainly located in the northeast of Portugal. This study provides better knowledge of their gastrointestinal parasitism, particularly strongyles, and the assessment of a targeted selective treatment (TST) as an alternative control approach of their parasitism. A longitudinal observational study was developed during a period of five years in a population of 62 Miranda donkeys. At first, strategic deworming of these animals was performed every semester, but this was progressively replaced by a TST approach according to the levels of Eggs per Gram (EPG). This new deworming strategy was conducted in association with a regular parasitological monitoring of the animals every three months, being dewormed with ivermectin when egg shedding was higher than 500 EPG. Over the study period, a decrease of the annual prevalence rate of infection by gastrointestinal strongyles was observed, from 35.5% to 19.4%, as well as a negative binomial distribution of parasitic strongyles in donkeys submitted to selective anthelminthic control. The prevalence rate of infection was higher in females (39.5%), in individuals under four years (46.7%) and in those presenting a lower body condition (40.8%). The egg output was higher in animals younger than four years (589.3 EPG) than in those older than 10 years (533.6 EPG) (
Toward a computational framework for cognitive biology: unifying approaches from cognitive neuroscience and comparative cognition.
Physics of life reviews, 2014

Progress in understanding cognition requires a quantitative, theoretical framework, grounded in the other natural sciences and able to bridge between implementational, algorithmic and computational levels of explanation. I review recent results in neuroscience and cognitive biology that, when combined, provide key components of such an improved conceptual framework for contemporary cognitive science. Starting at the neuronal level, I first discuss the contemporary realization that single neurons are powerful tree-shaped computers, which implies a reorientation of computational models of learning and plasticity to a lower, cellular, level. I then turn to predictive systems theory (predictive coding and prediction-based learning) which provides a powerful formal framework for understanding brain function at a more global level. Although most formal models concerning predictive coding are framed in associationist terms, I argue that modern data necessitate a reinterpretation of such models in cognitive terms: as model-based predictive systems. Finally, I review the role of the theory of computation and formal language theory in the recent explosion of comparative biological research attempting to isolate and explore how different species differ in their cognitive capacities. Experiments to date strongly suggest that there is an important difference between humans and most other species, best characterized cognitively as a propensity by our species to infer tree structures from sequential data. Computationally, this capacity entails generative capacities above the regular (finite-state) level; implementationally, it requires some neural equivalent of a push-down stack. I dub this unusual human propensity "dendrophilia", and make a number of concrete suggestions about how such a system may be implemented in the human brain, about how and why it evolved, and what this implies for models of language acquisition. I conclude that, although much remains to be done, a neurally-grounded framework for theoretical cognitive science is within reach that can move beyond polarized debates and provide a more adequate theoretical future for cognitive biology.
Pediatric transverse myelitis.
Neurology, 2016

Pediatric acute transverse myelitis (ATM) is an immune-mediated CNS disorder and contributes to 20% of children experiencing a first acquired demyelinating syndrome (ADS). ATM must be differentiated from other presentations of myelopathy and may be the first presentation of relapsing ADS such as neuromyelitis optica (NMO) or multiple sclerosis (MS). The tenets of the diagnostic criteria for ATM established by the Transverse Myelitis Consortium Working Group can generally be applied in children; however, a clear sensory level may not be evident in some. MRI lesions are often centrally located with high T2 signal intensity involving gray and neighboring white matter. Longitudinally extensive ATM occurs in the majority. Asymptomatic lesions on brain MRI are seen in more than one-third and predict MS or NMO. The role of antibodies such as myelin oligodendrocyte glycoprotein in monophasic and relapsing ATM and their significance in therapeutic approaches remain unclear. ATM is a potentially devastating condition with variable outcome and presents significant cumulative demands on health and social care resources. Children generally have a better outcome than adults, with one-half making a complete recovery by 2 years. There is need for standardization of clinical assessment and investigation protocols to enable international collaborative studies to delineate prognostic factors for disability and relapse. There are no robust controlled trials in children or adults to inform optimal treatment of ATM, with one study currently open to recruitment. This review provides an overview of current knowledge of clinical features, investigative workup, pathogenesis, and management of ATM and suggests future directions.