rudyvdbrink/CitationDatabase huggingface dataset:
Small Molecules and Peptides Targeting Glial Cell Line-Derived Neurotrophic Factor Receptors for the Treatment of Neurodegeneration.
International journal of molecular sciences, 2020

Glial cell line-derived neurotrophic factor (GDNF) family ligands (GFLs) are able to promote the survival of multiple neuronal populations in the body and, therefore, hold considerable promise for disease-modifying treatments of diseases and conditions caused by neurodegeneration. Available data reveal the potential of GFLs for the therapy of Parkinson's disease, neuropathic pain and diseases caused by retinal degeneration but, also, amyotrophic lateral sclerosis and, possibly, Alzheimer's disease. Despite promising data collected in preclinical models, clinical translation of GFLs is yet to be conducted. The main reasons for the limited success of GFLs clinical development are the poor pharmacological characteristics of GFL proteins, such as the inability of GFLs to cross tissue barriers, poor diffusion in tissues, biphasic dose-response and activation of several receptors in the organism in different cell types, along with ethical limitations on patients' selection in clinical trials. The development of small molecules selectively targeting particular GFL receptors with improved pharmacokinetic properties can overcome many of the difficulties and limitations associated with the clinical use of GFL proteins. The current review lists several strategies to target the GFL receptor complex with drug-like molecules, discusses their advantages, provides an overview of available chemical scaffolds and peptides able to activate GFL receptors and describes the effects of these molecules in cultured cells and animal models.
Gender Specific Characteristics of Revolving Door Adolescents in Acute Psychiatric Inpatient Care.
Child psychiatry and human development, 2018

This study examined the impact of clinical and family related factors on adolescent revolving door (RD) phenomenon, defined as having three or more psychiatric hospitalizations before the age of 18. A clinical sample of adolescents (N = 508) aged 13-17 years, admitted to psychiatric inpatient care between April 2001 through March 2006, were interviewed using the k-SADS-PL and the EuropASI instruments. The national Finnish Care Register for Health Care provided life-time data on child and adolescent psychiatric inpatient hospitalizations. RD boys were shown to be significantly more likely than non-RD boys to be admitted to psychiatric inpatient care from child welfare placements and have previous self-mutilative behavior (SMB) and suicide attempts. RD girls were more likely to come from child welfare placements, have unemployed mothers and a history of SMB. Mortality in RD boys was significantly higher compared to non-RD boys. Frequent use of psychiatric inpatient care warrants comprehensive assessment of suicidal behavior in adolescents.
Computer-based brief motivational intervention for perinatal drug use.
Journal of substance abuse treatment, 2005

Computer-based brief motivational interventions may be able to reach a high proportion of at-risk individuals and thus have potential for significant population impact. The present studies were conducted to determine the acceptability and preliminary efficacy of a computer-based brief motivational intervention (the motivation enhancement system, or MES). In Study 1, quantitative and qualitative feedback from 30 postpartum women and 17 women in treatment for drug use were used to modify the software. In Study 2, 50 urban postpartum women who reported drug use in the month before pregnancy completed the intervention and provided repeated within-session ratings of state motivation. In Study 3, 30 women were randomly assigned to intervention or control conditions with 1-month follow-up. Overall, women rated the MES as highly acceptable and easy to use and reported significant increases in state motivation at postintervention and at 1-month follow-up (d = .49). These preliminary results are encouraging and suggest that further work in this area is warranted.
Pathologic staging of white matter lesions in adult-onset leukoencephalopathy/leukodystrophy with axonal spheroids.
Journal of neuropathology and experimental neurology, 2015

The pathologic features of adult-onset leukoencephalopathy/leukodystrophy with axonal spheroids (ALAS) are variable, and this has led to different hypotheses as to whether primarily demyelination or axonopathy may underlie this disorder. Typical ALAS pathology is rarely accompanied by focal multiple sclerosis (MS)-like plaques. In ALAS pathology accompanied by focal multiple sclerosis (MS)-like plaques cases, the pathologic features cannot be distinguished from those of progressive MS with diffusely abnormal white matter. To clarify these issues, we examined neuropathologic features in 159 representative samples from 5 ALAS cases (3 men and 2 women aged 39-61 years) and in 95 representative samples from 3 chronic MS cases (1 man and 2 women aged 50-73 years). The white matter abnormalities in ALAS cases were characterized by 3 evolving stages: 1) white matter with numerous spheroids in a background of well-myelinated fibers; 2) moderate loss of myelinated fibers with sparse to moderate number of spheroids; and 3) leukodystrophy-like pattern of confluent axonal and myelin loss. The application of this staging system suggests that myelin loss in ALAS is preceded by axonopathy. In progressive MS cases, the diffusely abnormal white matter pathology could be attributed to both primary demyelination and axonopathy. Some cases with predominant axonopathy are difficult to distinguish from cases with ALAS.
Update on the ESCEO recommendation for the conduct of clinical trials for drugs aiming at the treatment of sarcopenia in older adults.
Aging clinical and experimental research, 2021

In 2016, an expert working group was convened under the auspices of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) and formulated consensus recommendations for the conduct of clinical trials for drugs to prevent or treat sarcopenia.
Diminishing fear: Optogenetic approach toward understanding neural circuits of fear control.
Pharmacology, biochemistry, and behavior, 2018

Understanding complex behavioral processes, both learned and innate, requires detailed characterization of the principles governing signal flow in corresponding neural circuits. Previous studies were hampered by the lack of appropriate tools needed to address the complexities of behavior-driving micro- and macrocircuits. The development and implementation of optogenetic methodologies revolutionized the field of behavioral neuroscience, allowing precise spatiotemporal control of specific, genetically defined neuronal populations and their functional connectivity both in vivo and ex vivo, thus providing unprecedented insights into the cellular and network-level mechanisms contributing to behavior. Here, we review recent pioneering advances in behavioral studies with optogenetic tools, focusing on mechanisms of fear-related behavioral processes with an emphasis on approaches which could be used to suppress fear when it is pathologically expressed. We also discuss limitations of these methodologies as well as review new technological developments which could be used in future mechanistic studies of fear behavior.
Investigation of optimal dose of early intervention to prevent posttraumatic stress disorder: A multiarm randomized trial of one and three sessions of modified prolonged exposure.
Depression and anxiety, 2020

Posttraumatic stress disorder (PTSD) is linked to a specific event, providing the opportunity to intervene in the immediate aftermath of trauma to prevent the development of this disorder. A previous trial demonstrated that trauma survivors who received three sessions of modified prolonged exposure therapy demonstrated decreased PTSD and depression prospectively compared to assessment only. The present study investigated the optimal dosing of this early intervention to test one versus three sessions of exposure therapy in the immediate aftermath of trauma.
The characteristics of the lobular arrangement indicate the dynamic role played by the infrapatellar fat pad in knee kinematics.
Journal of anatomy, 2019

The infrapatellar fat pad (IFP) is an intracapsular but extrasynovial structure, located between the patellar tendon, the femoral condyles and the tibial plateau. It consists of white adipose tissue, organised in lobules defined by thin connective septa. The aim of this study is the morphometric and ultrasonographic analysis of IFP in subjects without knee pathology during flexion-extension movements. The morphometric study was conducted on 20 cadavers (15M, 5F, mean age 80.2 years). Ultrasound was performed on 24 volunteers with no history of knee diseases (5M, 19F, mean age: 45 years). The characteristics of the adipose lobules near the patellar tendon and in the deep portion of the IFP were evaluated. Numerical models were provided, according to the size of the lobules. At histological examination, the adipose lobules located near the patellar tendon were larger (mean area 12.2 mm
Stress sounds the alarmin: The role of the danger-associated molecular pattern HMGB1 in stress-induced neuroinflammatory priming.
Brain, behavior, and immunity, 2015

High mobility group box-1 (HMGB1) is an endogenous danger signal or alarmin that mediates activation of the innate immune response including chemotaxis and pro-inflammatory cytokine release. HMGB1 has been implicated in the pathophysiology of several neuroinflammatory conditions including ischemia, traumatic brain injury, seizure and chronic ethanol use. In the present review, the unique structural and functional properties of HMGB1 will be explored including its affinity for multiple pattern recognition receptors (TLR2/TLR4), redox sensitivity and adjuvant-like properties. In light of recent evidence suggesting that HMGB1 may also mediate stress-induced sensitization of neuroinflammatory responses, mechanisms of HMGB1 action in neuroinflammatory priming are explored. A model of neuroinflammatory priming is developed wherein glucocorticoids induce synthesis and release of HMGB1 from microglia, which signals through TLR2/TLR4, thereby priming the NLRP3 inflammasome. We propose that if GCs reach a critical threshold as during a fight/flight response, they may thus function as an alarmin by inducing HMGB1, thereby preparing an organism's innate immune system (NLRP3 inflammasome priming) for subsequent immune challenges such as injury, trauma or infection, which are more likely to occur during a fight/flight response. In doing so, GCs may confer a significant survival advantage by enhancing the central innate immune and sickness response to immune challenges.
Harnessing networks and machine learning in neuropsychiatric care.
Current opinion in neurobiology, 2019

The development of next-generation therapies for neuropsychiatric illness will likely rely on a precise and accurate understanding of human brain dynamics. Toward this end, researchers have focused on collecting large quantities of neuroimaging data. For simplicity, we will refer to large cross-sectional neuroimaging studies as broad studies and to intensive longitudinal studies as deep studies. Recent progress in identifying illness subtypes and predicting treatment response in neuropsychiatry has been supported by these study designs, along with methods bridging machine learning and network science. Such methods combine analytic power, interpretability, and direct connection to underlying theory in cognitive neuroscience. Ultimately, we propose a general framework for the treatment of neuropsychiatric illness relying on the findings from broad and deep studies combined with basic cognitive and physiologic measurements.
Selective preservation of cholinergic MeCP2 rescues specific Rett-syndrome-like phenotypes in MeCP2
Behavioural brain research, 2017

RTT is a neurodevelopmental disorder characterized by growth regression, motor dysfunction, stereotypic hand movements, and autism features. Typical Rett syndrome (RTT) is predominantly caused by mutations in X-linked MeCP2 gene which encodes methyl-CpG-binding protein 2 (MeCP2). The brain-abundant MeCP2 protein mainly functions as a transcriptional regulator for neurodevelopment-associated genes. Specific functions of MeCP2 in certain neuron types remain to be known. Although cholinergic system is an important modulating system in brain, how MeCP2 in cholinergic neurons contribute to RTT has not been clearly understood. Here we use a mouse model with selectively activated endogenous MeCP2 in cholinergic neurons in otherwise MeCP2
Orbitofrontal control of visual cortex gain promotes visual associative learning.
Nature communications, 2020

The orbitofrontal cortex (OFC) encodes expected outcomes and plays a critical role in flexible, outcome-guided behavior. The OFC projects to primary visual cortex (V1), yet the function of this top-down projection is unclear. We find that optogenetic activation of OFC projection to V1 reduces the amplitude of V1 visual responses via the recruitment of local somatostatin-expressing (SST) interneurons. Using mice performing a Go/No-Go visual task, we show that the OFC projection to V1 mediates the outcome-expectancy modulation of V1 responses to the reward-irrelevant No-Go stimulus. Furthermore, V1-projecting OFC neurons reduce firing during expectation of reward. In addition, chronic optogenetic inactivation of OFC projection to V1 impairs, whereas chronic activation of SST interneurons in V1 improves the learning of Go/No-Go visual task, without affecting the immediate performance. Thus, OFC top-down projection to V1 is crucial to drive visual associative learning by modulating the response gain of V1 neurons to non-relevant stimulus.
Cognition, social cognition and functional disability in early-stage schizophrenia: A study from southern India.
Psychiatry research, 2018

In high-income countries a wealth of studies has revealed cognitive and social cognitive deficits in schizophrenia and a close relationship of these deficits to psychosocial functioning. Studies examining these illness features in middle and low-income countries are rare, particularly in early-stage samples. Sixty adult participants within 5 years of diagnosis with schizophrenia and 53 matched, healthy control were assessed with the MATRICS Consensus Cognitive Battery and the PEAT emotion identification task at study entry, and the WHODAS functioning scale one year later. Deficits on cognitive instruments ranged from d = 0.64-1.04 and were consistent with those reported in Western samples. Negative symptoms were linked to function longitudinally. Deficits in social cognitive skills and longitudinal links between cognition and functioning were not evident. These findings suggest a highly consistent magnitude of neurocognitive deficits in people with schizophrenia across widely varying cultures, but with limited evidence of social cognitive skill deficits using Western-based instruments. There was little evidence of a relationship between cognition and psychosocial disability in people with early-stage schizophrenia in this sample.
Brain comorbidities in normal pressure hydrocephalus.
European journal of neurology, 2018

This cross-sectional study aims to compare gait changes after the cerebrospinal fluid (CSF) tap test between normal pressure hydrocephalus patients with and without brain comorbidities (NPH+ and NPH- respectively) and then to identify significant contributors to a poor CSF tap test amongst individuals with NPH+.
Twin MRI studies on genetic and environmental determinants of brain morphology and function in the early lifespan.
Neuroscience and biobehavioral reviews, 2020

Neurodevelopment represents a period of increased opportunity and vulnerability, during which a complex confluence of genetic and environmental factors influences brain growth trajectories, cognitive and mental health outcomes. Recently, magnetic resonance imaging (MRI) studies on twins have increased our knowledge of the extent to which genes, the environment and their interactions shape inter-individual brain variability. The present review draws from highly salient MRI studies in young twin samples to provide a robust assessment of the heritability of structural and functional brain changes during development. The available studies suggest that (as with many other traits), global brain morphology and network organization are highly heritable from early childhood to young adulthood. Conversely, genetic correlations among brain regions exhibit heterogeneous trajectories, and this heterogeneity reflects the progressive, experience-related increase in brain network complexity. Studies also support the key role of environment in mediating brain network differentiation via changes of genetic expression and hormonal levels. Thus, rest- and task-related functional brain circuits seem to result from a contextual and dynamic expression of heritability.
Stereotyped terminal axon branching of leg motor neurons mediated by IgSF proteins DIP-α and Dpr10.
eLife, 2019

For animals to perform coordinated movements requires the precise organization of neural circuits controlling motor function. Motor neurons (MNs), key components of these circuits, project their axons from the central nervous system and form precise terminal branching patterns at specific muscles. Focusing on the
Biomarkers of CIDP in patients with diabetes or CMT1.
Journal of the peripheral nervous system : JPNS, 2011

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an autoimmune disease that targets the myelin sheaths in peripheral nerves. Primary demyelination can be detected by electrodiagnostic studies or nerve biopsy, but these do not distinguish between demyelination resulting from CIDP or from non-inflammatory causes such as diabetes or Charcot-Marie-Tooth type I. Consequently, the diagnosis of CIDP in such patients is often missed. Studies are needed to establish electrodiagnostic criteria for CIDP in patients with diabetes, and to identify biomarkers that distinguish between inflammatory and non-inflammatory causes of demyelinating neuropathy.
Sexually dimorphic behavioral and neural responses to a predator scent.
Behavioural brain research, 2020

Male and female C57BL/6 J mice were tested on the predator odor response task, where they needed to cross through a chamber of scented bedding to reach a sucrose reward. Following the behavioral testing, mouse brains were immunohistochemically labeled for expression of the immediate early gene c-fos. In the presence of the novel odorant methyl valerate (MV), both males and females exhibited increased exploration behaviors and delayed rewards compared to control bedding. However, in the presence of the predator odor phenylethylamine (PEA), males exhibited increased exploration that strongly resembled their behavior in MV (a non-predator odor) while females behaved very similarly to the clean bedding controls, quickly traversing the chamber to achieve the reward. Expression of c-fos exhibited significant sex by odor condition interactions overall across brain regions and in the anterior piriform cortex, cingulate cortex, and dorsomedial hypothalamus specifically. In all three regions we observed the general pattern that PEA exposure evoked elevated c-fos expression in females but suppressed c-fos expression in males. Taken together these data suggest that males and females may adopt different behavioral strategies in the presence of predator threat.
Gender and the use of hormonal contraception in women are not associated with cerebral cortical 5-HT 2A receptor binding.
Neuroscience, 2009

Gender influences brain function including serotonergic neurotransmission, which may play a role in the well-known gender variations in vulnerability to mood and anxiety disorders. Even though hormonal replacement therapy in menopause is associated with globally increased cerebral 5-HT(2A) receptor binding it is not clear if gender or use of hormonal contraception exhibits associations with 5-HT(2A) receptor binding. We found no significant effect of gender on cortical 5-HT(2A) receptor binding (P=0.15, n=132). When adjusting for the personality trait neuroticism, known to be positively correlated to frontolimbic 5-HT(2A) receptor binding and to be more pronounced in women, again, the effect of gender was not significant (P=0.42, n=127). Also, the use of hormonal contraception (n=14) within the group of pre-menopausal women (total n=29) was not associated with cortical 5-HT(2A) receptor binding (P=0.31). In conclusion, neither gender, nor the use of hormonal contraception in premenopausal women was associated with cortical 5-HT(2A) receptor binding.
Developmental attenuation of N-methyl-D-aspartate receptor subunit expression by microRNAs.
Neural development, 2015

N-methyl-D-aspartate receptors (NMDARs) are a subtype of ionotropic glutamate receptors and are expressed throughout the central nervous system (CNS). Their activity is required for excitatory synaptic transmission, the developmental refinement of neural circuits and for the expression of many forms of synaptic plasticity. NMDARs are obligate heterotetramers and the expression of their constituent subunits is developmentally and anatomically regulated. In rodent cortex and hippocampus, the GluN2B subunit is expressed at high levels early in development and decreases to plateau levels later while expression of the GluN2A subunit has a concomitant increase. Regulation of GluN2A and GluN2B expressions are incompletely understood. Here, we showed the influence of miRNAs in this process.
Bral1: "Superglue" for the extracellular matrix in the brain white matter.
The international journal of biochemistry & cell biology, 2012

Bral1 is a link protein that stabilizes the binding between lecticans and hyaluronic acid and thus maintains the extracellular matrix assembly in the CNS. Bral1 is specifically located in the white matter around the nodes of Ranvier. Recent studies suggest its function in promoting saltatory neural conduction. This article reviews the current knowledge about the structure, expression and function of this link protein.
Slit/Robo signaling mediates spatial positioning of spiral ganglion neurons during development of cochlear innervation.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013

During the development of periphery auditory circuits, spiral ganglion neurons (SGNs) extend their neurites to innervate cochlear hair cells (HCs) with their soma aggregated into a cluster spatially segregated from the cochlear sensory epithelium. The molecular mechanisms underlying this spatial patterning remain unclear. In this study, in situ hybridization in the mouse cochlea suggests that Slit2 and its receptor, Robo1/2, exhibit apparently complementary expression patterns in the spiral ganglion and its nearby region, the spiral limbus. In Slit2 and Robo1/2 mutants, the spatial restriction of SGNs was disrupted. Mispositioned SGNs were found to scatter in the space between the cochlear epithelium and the main body of spiral ganglion, and the neurites of mispositioned SGNs were misrouted and failed to innervate HCs. Furthermore, in Robo1/2 mutants, SGNs were displaced toward the cochlear epithelium as an entirety. Examination of different embryonic stages in the mutants revealed that the mispositioning of SGNs was due to a progressive displacement to ectopic locations after their initial normal settlement at an earlier stage. Our results suggest that Slit/Robo signaling imposes a restriction force on SGNs to ensure their precise positioning for correct SGN-HC innervations.