rudyvdbrink/CitationDatabase huggingface dataset:
Local "on-demand" generation and function of antigen-specific Foxp3+ regulatory T cells.
Journal of immunology (Baltimore, Md. : 1950), 2013

Extrathymically derived regulatory T cells (iTregs) protect against autoimmunity to tissue-specific Ags. However, whether Ag-specific iTreg generation and function is limited to secondary lymphoid tissue or whether it can occur within the tissue-specific local environment of the cognate Ag remains unresolved. Mice expressing β-galactosidase (βgal) on a retina-specific promoter (βgal mice) in conjunction with mice expressing GFP and diphtheria toxin (DTx) receptor (DTR) under control of the Foxp3 promoter, and βgal-specific TCR transgenic (BG2) mice were used to examine this question. Local depletion (ocular DTx), but not systemic depletion (i.p. DTx), of βgal-specific iTregs enhanced experimental autoimmune uveoretinitis induced by activated βgal-specific effector T cells. Injections of small amounts of βgal into the anterior chamber of the eye produced similar numbers of βgal-specific iTregs in the retina whether the mouse was depleted of pre-existing, circulating Tregs. Taken together, these results suggest that protection from tissue-specific autoimmunity depends on the function of local Ag-specific iTregs and that the retina is capable of local, "on-demand" iTreg generation that is independent of circulating Tregs.
Altered intrinsic connectivity distribution in internet gaming disorder and its associations with psychotherapy treatment outcomes.
Addiction biology, 2021

Alterations in brain connectivity have been implicated in internet gaming disorder (IGD). However, little is known about alterations in whole-brain connectivity and their associations with long-term treatment outcomes. Here, we used a relatively new analytic approach, intrinsic connectivity distribution (ICD) analysis, to examine brain connectivity in 74 IGD participants and 41 matched healthy controls (HCs) and conducted post hoc seed-based resting-state functional connectivity (rsFC) analyses based on the ICD findings. We also examined how these findings related to outcomes involving a craving behavioral intervention (CBI) for IGD. IGD participants showed less whole-brain connectivity in the left angular gyrus and ventromedial prefrontal cortex (vmPFC) compared with HC participants. Seed-based rsFC analyses revealed that the left angular gyrus in the IGD group showed less connectivity with areas involved in the default-mode network and greater connectivity with areas in the salience and executive control networks. CBI was associated with improved connectivity within regions in the default-mode network and regions across the default-mode and salience networks. ICD-identified connectivity differences in the left angular gyrus and vmPFC were related to changes in craving and severity of addiction 6 months after the intervention. The findings suggest that IGD is associated with alterations in brain connectivity that may be sensitive to interventions. Thus, the findings have implications for understanding mechanisms underlying CBI effects and for further treatment development.
The first international conference on SYNGAP1-related brain disorders: a stakeholder meeting of families, researchers, clinicians, and regulators.
Journal of neurodevelopmental disorders, 2018

Pathologic mutations in SYNGAP1 cause a genetically defined form of intellectual disability (ID) with comorbid epilepsy and autistic features. While only recently discovered, pathogenicity of this gene is a relatively frequent genetic cause of classically undefined developmental delay that progresses to ID with commonly occurring comorbidities.
The neurobiology of decision: consensus and controversy.
Neuron, 2009

We review and synthesize recent neurophysiological studies of decision making in humans and nonhuman primates. From these studies, the basic outline of the neurobiological mechanism for primate choice is beginning to emerge. The identified mechanism is now known to include a multicomponent valuation stage, implemented in ventromedial prefrontal cortex and associated parts of striatum, and a choice stage, implemented in lateral prefrontal and parietal areas. Neurobiological studies of decision making are beginning to enhance our understanding of economic and social behavior as well as our understanding of significant health disorders where people's behavior plays a key role.
cAMP-dependent axon guidance is distinctly regulated by Epac and protein kinase A.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2009

cAMP is a key mediator of a number of molecules that induce growth cone chemotaxis, including netrin-1 and myelin-associated glycoprotein (MAG). Endogenous neuronal cAMP levels decline during development, and concomitantly axonal growth cones switch their response to cAMP-dependent guidance cues from attraction to repulsion. The mechanisms by which cAMP regulates these polarized growth cone responses are unknown. We report that embryonic growth cone attraction to gradients of cAMP, netrin-1, or MAG is mediated by Epac. Conversely, the repulsion conferred by MAG or netrin-1 on adult growth cones is mediated by protein kinase A (PKA). Furthermore, fluorescence resonance energy transfer reveals that netrin-1 distinctly activates Epac in embryonic growth cones but PKA in postnatal neurons. Our results suggest that cAMP mediates growth cone attraction or repulsion by distinctly activating Epac or PKA, respectively. Moreover, we propose that the developmental switch in growth cone response to gradients of cAMP-dependent guidance cues from attraction to repulsion is the result of a switch from Epac- to PKA-mediated signaling pathways.
Muscle pain syndromes and fibromyalgia: the role of muscle biopsy.
Current opinion in supportive and palliative care, 2018

Muscle pain syndromes are extremely frequent cause of chronic disability, and a muscle biopsy is often performed to achieve a diagnosis when myalgia has a myopatic origin. Instead, the role of muscle biopsy in fibromyalgia is controversial. This review examines the reported studies with the objective to evaluate if some changes exist in the muscle, if these changes produce pain and if muscle biopsy is helpful in diagnostic flowchart of fibromyalgia.
Life science-based neuroscience education at large Western Public Universities.
Journal of neuroscience research, 2016

The last 40 years have seen a remarkable increase in the teaching of neuroscience at the undergraduate level. From its origins as a component of anatomy or physiology departments to its current status as an independent interdisciplinary field, neuroscience has become the chosen field of study for many undergraduate students, particularly for those interested in medical school or graduate school in neuroscience or related fields. We examined how life science-based neuroscience education is offered at large public universities in the Western United States. By examining publicly available materials posted online, we found that neuroscience education may be offered as an independent program, or as a component of biological or physiological sciences at many institutions. Neuroscience programs offer a course of study involving a core series of courses and a collection of topical electives. Many programs provide the opportunity for independent research, or for laboratory-based training in neuroscience. Features of neuroscience programs at Western universities closely matched those seen at the top 25 public universities, as identified by U.S. News & World Report. While neuroscience programs were identified in many Western states, there were several states in which public universities appeared not to provide opportunities to major in neuroscience. © 2016 Wiley Periodicals, Inc.
Peripheral nerve diffusion tensor imaging as a measure of disease progression in ALS.
Journal of neurology, 2017

Clinical trial design in amyotrophic lateral sclerosis (ALS) remains hampered by a lack of reliable and sensitive biomarkers of disease progression. The present study evaluated peripheral nerve diffusion tensor imaging (DTI) as a surrogate marker of axonal degeneration in ALS. Longitudinal studies were undertaken in 21 ALS patients studied at 0 and 3 months, and 19 patients at 0, 3 and 6 months, with results compared to 13 age-matched controls. Imaging metrics were correlated across a range of functional assessments including amyotrophic lateral sclerosis functional rating scale revised (ALSFRS-R), lower limb muscle strength (Medical Research Council sum score, MRCSS-LL), compound muscle action potential amplitudes and motor unit number estimation (MUNE). Fractional anisotropy was reduced at baseline in ALS patients in the tibial (p < 0.05), and peroneal nerve (p < 0.05). Fractional anisotropy and axial diffusivity declined in the tibial nerve between baselines, 3- and 6-month scans (p < 0.01). From a functional perspective, ALSFRS-R correlated with fractional anisotropy values from tibial (R = 0.75, p < 0.001) and peroneal nerves (R = 0.52, p = 0.001). Similarly, peroneal nerve MUNE values correlated with fractional anisotropy values from the tibial (R = 0.48, p = 0.002) and peroneal nerve (R = 0.39, p = 0.01). There were correlations between the change in ALSFRS-R and tibial nerve axial diffusivity (R = 0.38, p = 0.02) and the change in MRCSS-LL and peroneal nerve fractional anisotropy (R = 0.44, p = 0.009). In conclusion, this study has demonstrated that some peripheral nerve DTI metrics are sensitive to axonal degeneration in ALS. Further, that DTI metrics correlated with measures of functional disability, strength and neurophysiological measures of lower motor neuron loss.
Neurochemistry of the afferents to the rat cochlear root nucleus: possible synaptic modulation of the acoustic startle.
Neuroscience, 2008

Afferents to the primary startle circuit are essential for the elicitation and modulation of the acoustic startle reflex (ASR). In the rat, cochlear root neurons (CRNs) comprise the first component of the acoustic startle circuit and play a crucial role in mediating the ASR. Nevertheless, the neurochemical pattern of their afferents remains unclear. To determine the distribution of excitatory and inhibitory inputs, we used confocal microscopy to analyze the immunostaining for vesicular glutamate and GABA transporter proteins (VGLUT1 and VGAT) on retrogradely labeled CRNs. We also used reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry to detect and localize specific neurotransmitter receptor subunits in the cochlear root. Our results show differential distributions of VGLUT1- and VGAT-immunoreactive endings around cell bodies and dendrites. The RT-PCR data showed a positive band for several ionotropic glutamate receptor subunits, M1-M5 muscarinic receptor subtypes, the glycine receptor alpha1 subunit (GlyRalpha1), GABAA, GABAB, and subunits of alpha2 and beta-noradrenergic receptors. By immunohistochemistry, we confirmed that CRN cell bodies exhibit positive immunoreaction for the glutamate receptor (GluR) 3 and NR1 GluR subunits. Cell bodies and dendrites were also positive for M2 and M4, and GlyRalpha1. Other subunits, such as GluR1 and GluR4 of the AMPA GluRs, were observed in glial cells neighboring unlabeled CRN cell bodies. We further confirmed the existence of noradrenergic afferents onto CRNs from the locus coeruleus by combining tyrosine hydroxylase immunohistochemistry and tract-tracing experiments. Our results provide valuable information toward understanding how CRNs might integrate excitatory and inhibitory inputs, and hence how they could elicit and modulate the ASR.
Hippocampal neural correlates for values of experienced events.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012

Newly experienced events are often remembered together with how rewarding the experiences are personally. Although the hippocampus is a candidate structure where subjective values are integrated with other elements of episodic memory, it is uncertain whether and how the hippocampus processes value-related information. We examined how activity of dorsal CA1 and dorsal subicular neurons in rats performing a dynamic foraging task was related to reward values that were estimated using a reinforcement learning model. CA1 neurons carried significant signals related to action values before the animal revealed its choice behaviorally, indicating that the information on the expected values of potential choice outcomes was available in CA1. Moreover, after the outcome of the animal's goal choice was revealed, CA1 neurons carried robust signals for the value of chosen action and they temporally overlapped with the signals related to the animal's goal choice and its outcome, indicating that all the signals necessary to evaluate the outcome of an experienced event converged in CA1. On the other hand, value-related signals were substantially weaker in the subiculum. These results suggest a major role of CA1 in adding values to experienced events during episodic memory encoding. Given that CA1 neuronal activity is modulated by diverse attributes of an experienced event, CA1 might be a place where all the elements of episodic memory are integrated.
Mitochondria-Targeted Small Peptide, SS31 Ameliorates Diabetes Induced Mitochondrial Dynamics in Male TallyHO/JngJ Mice.
Molecular neurobiology, 2021

The escalating burden of type 2 diabetes (T2D) and its related complications has become a major public health challenge worldwide. Substantial evidence indicates that T2D is one of the culprits for the high prevalence of Alzheimer's disease (AD) in diabetic subjects. This study aimed to investigate the possible mitochondrial alterations in the pancreas induced by hyperglycemia in diabetes. We used a diabetic TallyHO/JngJ (TH) and non-diabetic, SWR/J mice strains. The diabetic and non-diabetic status in animals was assessed by performing intraperitoneal glucose tolerance test at four time points, i.e., 4, 8, 16, and 24 weeks of age. We divided 24-week-old TH and SWR/J mice into 3 groups: controls, diabetic TH mice, and diabetic TH mice treated with SS31 peptide. After the treatment of male TH mice with SS31, intraperitoneally, for 4 weeks, we studied mitochondrial dynamics, biogenesis, and function. The mRNA and protein expression levels of mitochondrial proteins were evaluated using qPCR and immunoblot analysis. The diabetic mice after 24 weeks of age showed overt pancreatic injury as demonstrated by disintegration and atrophy of β cells with vacuolization and reduced islet size. Mitochondrial dysfunction was observed in TH mice, as evidenced by significantly elevated H
Overview of Nrf2 as Therapeutic Target in Epilepsy.
International journal of molecular sciences, 2015

Oxidative stress is a biochemical state of imbalance in the production of reactive oxygen and nitrogen species and antioxidant defenses. It is involved in the physiopathology of degenerative and chronic neuronal disorders, such as epilepsy. Experimental evidence in humans and animals support the involvement of oxidative stress before and after seizures. In the past few years, research has increasingly focused on the molecular pathways of this process, such as that involving transcription factor nuclear factor E2-related factor 2 (Nrf2), which plays a central role in the regulation of antioxidant response elements (ARE) and modulates cellular redox status. The aim of this review is to present experimental evidence on the role of Nrf2 in this neurological disorder and to further determine the therapeutic impact of Nrf2 in epilepsy.
Mitophagy and Alzheimer's Disease: Cellular and Molecular Mechanisms.
Trends in neurosciences, 2017

Neurons affected in Alzheimer's disease (AD) experience mitochondrial dysfunction and a bioenergetic deficit that occurs early and promotes the disease-defining amyloid beta peptide (Aβ) and Tau pathologies. Emerging findings suggest that the autophagy/lysosome pathway that removes damaged mitochondria (mitophagy) is also compromised in AD, resulting in the accumulation of dysfunctional mitochondria. Results in animal and cellular models of AD and in patients with sporadic late-onset AD suggest that impaired mitophagy contributes to synaptic dysfunction and cognitive deficits by triggering Aβ and Tau accumulation through increases in oxidative damage and cellular energy deficits; these, in turn, impair mitophagy. Interventions that bolster mitochondrial health and/or stimulate mitophagy may therefore forestall the neurodegenerative process in AD.
Inhibition of spinal cytosolic phospholipase A(2) expression by an antisense oligonucleotide attenuates tissue injury-induced hyperalgesia.
Neuroscience, 2008

Activation of the spinal phospholipase A(2) (PLA(2)) -cyclooxygenase (COX) -prostaglandin signaling pathway is widely implicated in nociceptive processing. Although the role of spinal COX isoforms in pain signal transmission has been extensively characterized, our knowledge of PLA(2) enzymes in this cascade is limited. Among all PLA(2) groups, cytosolic calcium-dependent PLA(2) group IVA (cPLA(2)IVA) appears to be the predominant PLA(2) enzyme in the spinal cord. In the present study we sought to (i) characterize anatomical and cellular distribution and localization of cPLA(2)IVA in dorsal horn of rat spinal cord, (ii) verify efficacy and selectivity of intrathecal (IT) delivery of an antisense oligonucleotide (AS) targeting rat cPLA(2)IVA mRNA on spinal expression of this enzyme, and (iii) examine the effect of down-regulation of spinal cPLA(2)IVA on peripheral tissue injury-induced pain behavior. Here we demonstrate that cPLA(2)IVA is constitutively expressed in rat spinal cord, predominantly in dorsal horn neurons and oligodendrocytes but not in astrocytes or microglia. Intrathecal injection of AS significantly down-regulated both protein and gene expression of cPLA(2)IVA in rat spinal cord, while control missense oligonucleotide (MS) had no effect. Immunocytochemistry confirmed that the reduction occurred in neurons and oligodendrocytes. cPLA(2)IVA AS did not alter expression of several other PLA(2) isoforms, such as secretory PLA(2) (groups IIA and V) and calcium-independent PLA(2) (group VI), indicating that the AS was specific for cPLA(2)IVA. This selective knockdown of spinal cPLA(2)IVA did not change acute nociception (i.e. paw withdrawal thresholds to acute thermal stimuli and intradermal formalin-induced first phase flinching), however, it significantly attenuated formalin-induced hyperalgesia (i.e. second phase flinching behavior), which reflects spinal sensitization. Thus the present findings suggest that cPLA(2)IVA may specifically participate in spinal nociceptive processing.
Drinking to cope with depression mediates the relationship between social avoidance and alcohol problems: A 3-wave, 18-month longitudinal study.
Addictive behaviors, 2018

Undergraduates with high social anxiety have increased alcohol problems, despite lower or equivalent alcohol use levels. Drinking motives mediate the cross-sectional relationship between social anxiety and alcohol problems, with coping and conformity motives being the most commonly observed mediators. Our study extended prior research by using a longitudinal design, examining coping with anxiety motives (CAM) and coping with depression motives (CDM) separately using path analysis, simultaneously considering a variety of drinking motives in the model, and focusing on a particularly severe form of social anxiety - namely, social avoidance. We collected data from 219 undergraduates (72.6% women, mean age of 20.59years) over three waves spaced six months apart. Results indicated CDM mediated the prospective relationship between social avoidance and alcohol problems. Findings suggest socially avoidant students' escalations in CDM explain their increased alcohol problems over time. Future research should examine involvement of depression and social isolation in contributing to this pathway to alcohol problems.
Sex and genetic differences in the effects of acute diesel exhaust exposure on inflammation and oxidative stress in mouse brain.
Toxicology, 2016

In addition to increased morbidity and mortality caused by respiratory and cardiovascular diseases, air pollution may also contribute to central nervous system (CNS) diseases. Traffic-related air pollution is a major contributor to global air pollution, and diesel exhaust (DE) is its most important component. DE contains more than 40 toxic air pollutants and is a major constituent of ambient particulate matter (PM), particularly of ultrafine-PM. Limited information suggests that exposure to DE may cause oxidative stress and neuroinflammation in the CNS. We hypothesized that males may be more susceptible than females to DE neurotoxicity, because of a lower level of expression of paraoxonase 2 (PON2), an intracellular anti-oxidant and anti-inflammatory enzyme. Acute exposure of C57BL/6 mice to DE (250-300μg/m
Indicators of vulnerability associated with less healthy circadian rhythms in undergraduate medical interns.
Chronobiology international, 2019

To evaluate the association between circadian health parameters and psychological and biological vulnerability, a cross-sectional study was conducted with 15 undergraduate medical interns using the Brief Resilience Scale, the Mini International Neuropsychiatric Interview, and an ambulatory circadian monitoring device. Circadian Health construct was confirmed by factor analysis. Vulnerability factors (history of depression and low resilience) were associated to lower circadian health of motor activity and temperature rhythms. The findings suggest that not only being depressed but also having had depressive episodes in the past, as well as having low resilience, are associated with chronodisruption, and may increase the risk for developing new episodes of depression.
Salubrious effects of oxytocin on social stress-induced deficits.
Hormones and behavior, 2012

Social relationships are a fundamental aspect of life, affecting social, psychological, physiological, and behavioral functions. While positive social interactions can attenuate stress and promote health, the social environment can also be a major source of stress when it includes social disruption, confrontation, isolation, or neglect. Social stress can impair the basal function and stress-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis, impairing function of multiple biological systems and posing a risk to mental and physical health. In contrast, social support can ameliorate stress-induced physiological and immunological deficits, reducing the risk of subsequent psychological distress and improving an individual's overall well-being. For better clinical treatment of these physiological and mental pathologies, it is necessary to understand the regulatory mechanisms of stress-induced pathologies as well as determine the underlying biological mechanisms that regulate social buffering of the stress system. A number of ethologically relevant animal models of social stress and species that form strong adult social bonds have been utilized to study the etiology, treatment, and prevention of stress-related disorders. While undoubtedly a number of biological pathways contribute to the social buffering of the stress response, the convergence of evidence denotes the regulatory effects of oxytocin in facilitating social bond-promoting behaviors and their effect on the stress response. Thus, oxytocin may be perceived as a common regulatory element of the social environment, stress response, and stress-induced risks on mental and physical health. This article is part of a Special Issue entitled Oxytocin, Vasopressin, and Social Behavior.