rudyvdbrink/CitationDatabase huggingface dataset:
GSK-3β activation is required for ZIP-induced disruption of learned fear.
Scientific reports, 2020

The myristoylated zeta inhibitory peptide (ZIP), which was originally developed as a protein kinase C/Mζ (PKCζ/PKMζ) inhibitor, is known to produce the loss of different forms of memories. However, ZIP induces memory loss even in the absence of PKMζ, and its mechanism of action, therefore, remains elusive. Here, through a kinome-wide screen, we found that glycogen synthase kinase 3 beta (GSK-3β) was robustly activated by ZIP in vitro. ZIP induced depotentiation (a cellular substrate of memory erasure) of conditioning-induced potentiation at LA synapses, and the ZIP-induced depotentiation was prevented by a GSK-3β inhibitor, 6-bromoindirubin-3-acetoxime (BIO-acetoxime). Consistently, GSK-3β inhibition by BIO-acetoxime infusion or GSK-3β knockdown by GSK-3β shRNA in the LA attenuated ZIP-induced disruption of learned fear. Furthermore, conditioned fear was decreased by expression of a non-inhibitable form of GSK-3β in the LA. Our findings suggest that GSK-3β activation is a critical step for ZIP-induced disruption of memory.
Hungry to gamble? Ghrelin as a predictor of persistent gambling in the face of loss.
Biological psychology, 2018

Ghrelin, a peptide hormone associated with appetite, is also linked to increased reward seeking behaviors, including food, sex, and drug seeking behaviors through the stimulation of the mesolimbic dopaminergic system. Moreover, plasma ghrelin concentrations are increased by cues that predict rewards, suggesting that cues could facilitate cravings and ultimately relapse. In this project we examined the effects of an overnight fast, a manipulation known to increase ghrelin concentrations, on gambling behaviors. We also examined if cues associated with gambling would also increase ghrelin and, if so, we examined if these increases were associated with gambling behavior. One hundred and one (37 females) participants were asked to fast overnight or after breakfast and then asked to complete food and gambling craving questionnaires. Participants were then presented with gambling cues (a casino like environment in the lab) or a control cue (a cubicle with a computer). After the cue, subjects filled gambling craving questionnaires, and were allowed to gamble. Following 25 practice spins, the slot machines were fixed so that all subsequent spins were losses, and the number of spins in spite of losses were quantified. Blood samples were collected throughout the experiment. Results showed that the gambling cues significantly increased ghrelin concentrations particularly in fasted individuals, and that ghrelin concentrations 20 min after the cue were the best predictor for gambling persistence in the face of continued loss (p < 0.05). Our results suggest that cues that predict the opportunity to gamble have an acute effect on ghrelin concentrations that is facilitated by fasting, and that ghrelin concentrations are a significant predictor of gambling persistence.
Novel Therapeutic Approach for Excitatory/Inhibitory Imbalance in Neurodevelopmental and Neurodegenerative Diseases.
Annual review of pharmacology and toxicology, 2021

Excitatory/inhibitory (E/I) balance, defined as the balance between excitation and inhibition of synaptic activity in a neuronal network, accounts in part for the normal functioning of the brain, controlling, for example, normal spike rate. In many pathological conditions, this fine balance is perturbed, leading to excessive or diminished excitation relative to inhibition, termed E/I imbalance, reflected in network dysfunction. E/I imbalance has emerged as a contributor to neurological disorders that occur particularly at the extremes of life, including autism spectrum disorder and Alzheimer's disease, pointing to the vulnerability of neuronal networks at these critical life stages. Hence, it is important to develop approaches to rebalance neural networks. In this review, we describe emerging therapies that can normalize the E/I ratio or the underlying abnormality that contributes to the imbalance in electrical activity, thus improving neurological function in these maladies.
Adolescent MDMA exposure diminishes the physiological and neurotoxic consequences of an MDMA binge in female rats.
Developmental psychobiology, 2014

Intermittent MDMA pretreatment blocked the reductions in serotonin transporter (SERT) binding induced by an MDMA binge in a prior study in adolescent male rats. The objective of this investigation was to determine if the physiological, behavioral, and neurochemical responses to MDMA are sexually dimorphic. Female Sprague-Dawley rats received MDMA (10 mg/kg × 2) or Saline on every fifth day from postnatal day (PD) 35-60 and an MDMA binge (5 mg/kg × 4) on PD 67. The MDMA binge induced a pronounced temperature dysregulation in MDMA-naïve, but not MDMA-pretreated, groups. Similarly, MDMA-pretreated animals were resistant to the binge-induced SERT reductions, especially in the hippocampus. Motor activity at PD 68 was not reduced by the binge, unlike the responses found in males. These results show that female rats differ from males in their responses to an MDMA binge but are similar with respect to preconditioning from prior MDMA exposure.
A breath of new life into human social cognition.
Chemical senses, 2014

Sniffing has historically been considered an olfactory behavior because inhalation is a necessary step in odor perception. Growing evidence, however, has demonstrated that the display of sniffing surpasses the bounds of those contexts that are olfactory in nature. In this issue of Chemical Senses, Arzi, Shedlesky, Secundo, and Sobel demonstrate that humans mimic visually and auditory-observed sniffing, independent of experimentally applied olfactory sensory input. These findings raise important and exciting questions about the possible roles of sniffing in the social context and highlight the need for chemosensory researchers to reconsider the significance of sniffing.
Applying network analysis to investigate the links between dimensional schizotypy and cognitive and affective empathy.
Journal of affective disorders, 2020

Although impairment in empathy has been reported in schizophrenia spectrum disorders, little is known about the relationship between empathy and schizotypal traits. This study examines this relationship by applying network analysis to a large sample collected at 18-months follow-up in a longitudinal dataset.
Different effects of etomidate and propofol on memory in immature rats.
The International journal of neuroscience, 2015

This study is to investigate the effects of etomidate and propofol on memory and possible involved mechanisms using immature rats. Forty-eight rats randomly received intraperitoneal injection of 5 mg/kg etomidate (n = 16), 50 mg/kg propofol (n = 16) or normal saline (control, n = 16). Three hours after awakening, memory was assessed by Y-maze test using 10 rats in each drug group. Gamma-aminobutyric acid (GABA) content in hippocampal tissue was measured using six rats in each group. Etomidate group had more total reaction time (TRT) compared with the control group in Y-maze test ( p < 0.05). No other difference between these two groups was observed. Propofol group had less number of correct response ( p < 0.01) and more TRT ( p < 0.05) in Y-maze test, as well as more GABA concentration detected in hippocampal tissue ( p < 0.01) than the control group. Propofol group also showed less number of correct response ( p < 0.05) and more hippocampal GABA concentration ( p < 0.01) compared with etomidate group. Etomidate does not show significant effects on memory in rat and further investigation is required. Propofol can affect memory in rat possibly via increasing the synthesis and/or secretion of GABA as one of the factors.
NEUROCYSTICERCOSIS - A CLINICOPATHOLOGICAL APPRAISAL.
Medical journal, Armed Forces India, 1998

Neurocysticercosis is the most common parasitic disease affecting the human central nervous system, with protean clinical manifestations. During the last 17 years, 153 cases of neurocysticercosis were histopathologically diagnosed on surgically resected and autopsied material. Variable number of cysts, from a solitary one to multiple were found invading different parts of the neuraxis (118 cases). These cestode larval forms had a prediliction for locating in the cerebral grey matter (98 cases), followed by subcortical nuclear area (12), cerebral ventricles and subarachnoid cisterns (26 cases). Patients harbouring parenchymal cysts manifested predominantly with seizures and encephalitis (113 cases) whereas those with ventricular and/or cisternal cysts presented with features of chronic meningitis and hydrocephalus. The unusual clinical presentations were psychiatric symptoms with behavioural abnormalities and stroke in the young as a result of cysticercal meningitis with associated arteritis. Primary cysticercal abscess in the brain parenchyma was an interesting pathological feature noted in 3 cases. In the endemic areas, the co-existence of neurocysticercosis appears to enhance the morbidity and mortality due to Japanese encephalitis (31 cases). The surface glycoprotein of the cysticercal cyst has been identified to be the antigenic component to which the host immune system responds by forming antibody in the CSF.
Multi-aspect testing and ranking inference to quantify dimorphism in the cytoarchitecture of cerebellum of male, female and intersex individuals: a model applied to bovine brains.
Brain structure & function, 2020

The dimorphism among male, female and freemartin intersex bovines, focusing on the vermal lobules VIII and IX, was analyzed using a novel data analytics approach to quantify morphometric differences in the cytoarchitecture of digitalized sections of the cerebellum. This methodology consists of multivariate and multi-aspect testing for cytoarchitecture-ranking, based on neuronal cell complexity among populations defined by factors, such as sex, age or pathology. In this context, we computed a set of shape descriptors of the neural cell morphology, categorized them into three domains named size, regularity and density, respectively. The output and results of our methodology are multivariate in nature, allowing an in-depth analysis of the cytoarchitectonic organization and morphology of cells. Interestingly, the Purkinje neurons and the underlying granule cells revealed the same morphological pattern: female possessed larger, denser and more irregular neurons than males. In the Freemartin, Purkinje neurons showed an intermediate setting between males and females, while the granule cells were the largest, most regular and dense. This methodology could be a powerful instrument to carry out morphometric analysis providing robust bases for objective tissue screening, especially in the field of neurodegenerative pathologies.
Vorinostat and fenretinide synergize in preclinical models of T-cell lymphoid malignancies.
Anti-cancer drugs, 2021

T-cell lymphoid malignancies (TCLMs) are in need of novel and more effective therapies. The histone deacetylase (HDAC) inhibitors and the synthetic cytotoxic retinoid fenretinide have achieved durable clinical responses in T-cell lymphomas as single agents, and patients who failed prior HDAC inhibitor treatment have responded to fenretinide. We have previously shown fenretinide synergized with the class I HDAC inhibitor romidepsin in preclinical models of TCLMs. There exist some key differences between HDAC inhibitors. Therefore, we determined if the pan-HDAC inhibitor vorinostat synergizes with fenretinide. We demonstrated cytotoxic synergy between vorinostat and fenretinide in nine TCLM cell lines at clinically achievable concentrations that lacked cytotoxicity for non-malignant cells (fibroblasts and blood mononuclear cells). In vivo, vorinostat + fenretinide + ketoconazole (enhances fenretinide exposures by inhibiting fenretinide metabolism) showed greater activity in subcutaneous TCLM xenograft models than other groups. Fenretinide + vorinostat increased reactive oxygen species (ROS, measured by 2',7'-dichlorodihydrofluorescein diacetate dye), resulting in increased apoptosis (via transferase dUTP nick end labeling assay) and histone acetylation (by immunoblotting). The synergistic cytotoxicity, apoptosis, and histone acetylation of fenretinide + vorinostat was abrogated by the antioxidant vitamin C. Like romidepsin, vorinostat combined with fenretinide achieved synergistic cytotoxic activity and increased histone acetylation in preclinical models of TCLMs, but not in non-malignant cells. As vorinostat is an oral agent and not a P-glycoprotein substrate it may have advantages in such combination therapy. These data support conducting a clinical trial of vorinostat combined with fenretinide in relapsed and refractory TCLMs.
Accrual of functional redundancy along the lifespan and its effects on cognition.
NeuroImage, 2021

Despite the necessity to understand how the brain endures the initial stages of age-associated cognitive decline, no brain mechanism has been quantitatively specified to date. The brain may withstand the effects of cognitive aging through redundancy, a design feature in engineered and biological systems, which entails the presence of substitute elements to protect it against failure. Here, we investigated the relationship between functional network redundancy and age over the human lifespan and their interaction with cognition, analyzing resting-state functional MRI images and cognitive measures from 579 subjects. Network-wide redundancy was significantly associated with age, showing a stronger link with age than other major topological measures, presenting a pattern of accumulation followed by old-age decline. Critically, redundancy significantly mediated the association between age and executive function, with lower anti-correlation between age and cognition in subjects with high redundancy. The results suggest that functional redundancy accrues throughout the lifespan, mitigating the effects of age on cognition.
Auditory and Visual System White Matter Is Differentially Impacted by Normative Aging in Macaques.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2020

Deficits in auditory and visual processing are commonly encountered by older individuals. In addition to the relatively well described age-associated pathologies that reduce sensory processing at the level of the cochlea and eye, multiple changes occur along the ascending auditory and visual pathways that further reduce sensory function in each domain. One fundamental question that remains to be directly addressed is whether the structure and function of the central auditory and visual systems follow similar trajectories across the lifespan or sustain the impacts of brain aging independently. The present study used diffusion magnetic resonance imaging and electrophysiological assessments of auditory and visual system function in adult and aged macaques to better understand how age-related changes in white matter connectivity at multiple levels of each sensory system might impact auditory and visual function. In particular, the fractional anisotropy (FA) of auditory and visual system thalamocortical and interhemispheric corticocortical connections was estimated using probabilistic tractography analyses. Sensory processing and sensory system FA were both reduced in older animals compared with younger adults. Corticocortical FA was significantly reduced only in white matter of the auditory system of aged monkeys, while thalamocortical FA was lower only in visual system white matter of the same animals. Importantly, these structural alterations were significantly associated with sensory function within each domain. Together, these results indicate that age-associated deficits in auditory and visual processing emerge in part from microstructural alterations to specific sensory white matter tracts, and not from general differences in white matter condition across the aging brain.
The diagnostic iter of patent foramen ovale in migraine patients: an update.
Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 2008

Patent foramen ovale (PFO) is a frequent finding in migraine patients. The standard technique for PFO diagnosis is actually trans-oesophageal echocardiography (TEE). It requires the injection of a contrast agent unable to pass the pulmonary filter; hence, it is possible to detect a right-to-left shunt by observing the presence of the contrast medium in the cardiac left compartment. The transcranial Doppler (TCD) device accurately measures the blood flow velocities in different cerebral arteries. It can record microembolic signals (MES) backscattered by microbubbles travelling in the cerebral circulation, and distinguish cardiac shunts from pulmonary shunts. The number of MES is correlated to the entity of the shunt. The near-infrared spectroscopy (NIRS) technique tracks the changes in the concentration of oxygenated and reduced haemoglobin in the brain tissue. PFO is revealed by an alteration of the normal vasoreactivity pattern of the subject during functional stimuli. Magnetic resonance imaging (MRI) provides, at the same time, detailed anatomical information and functional measurements. MRI dynamic perfusion sequences can be used to reliably detect PFO either by visual assessment or by signal-time curves in the pulmonary artery and in the left atrium. A good correlation between TEE and MRI grading scores has been demonstrated, even though the interindividual variability of performing the Valsalva manoeuvre could greatly reduce the sensitivity of the method. Further prospective studies are needed to confirm the PFO MRI grading and to assess the sensitivity and specificity of the method.
Medical Education, Pre- and Post-Pandemic Era: A Review Article.
Cureus, 2020

A pandemic is the worldwide outbreak and spread of a disease. Although pandemics of influenza have occurred rarely, approximately once every few decades in more than three centuries, the outbreaks of H1N1 and H5N1 influenza, the severe acute respiratory syndrome (SARS), and most recently, the novel coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have necessitated the institution of protective and preventive measures such as school closure and mandatory quarantine of infected people, as social distancing is considered to be the most effective preventative strategy until the development of a vaccine, treatment, or both. The current pandemic has also resulted in a transformation in medical education for both undergraduate and postgraduate medical students. Clinical rotations for undergraduates have been suspended all over the world; inter-hospital residency rotations and combined teaching sessions have also been curtailed until further notice. During this most recent pandemic, a number of medical schools have immediately converted their whole clinical curriculum into online formats. Similarly, educational and clinical assessments have been converted into online assessments. However, as the pandemic eras tend to recur over time and epidemics will continue to break out, medical students and healthcare workers will remain susceptible to contagion. Hence, we need to adopt a new educational system that would be safe and sustainable in the long run.
Cellular stage specific functional analysis of REX1: In human embryonic stem cells.
Proteomics, 2015

As transcription and translation are dynamic and can vary among the cell types and conditions, proteomics may reveal the tissue-specific functions of a protein, more relevant to its genuine functions on cellular mechanisms. The new proteome analysis by Son et al. [Proteomics 2015, 15, 2220-2229] identified the functions of the pluripotency marker protein, REX1 in hESCs, and unraveling its regulatory network orchestrating pluripotency. Compared to the previous transcriptome analysis that showed mechanisms irrelevant to pluripotency, Son et al. employed a proteome analysis determined convincing and meaningful mechanisms of REX. In addition to demonstrating the biological importance of REX1, this research by Son et al. is also a compelling example of the conceptual significance of connecting proteomics with stem cell biology.
Linking Social Cognition to Learning and Memory.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2020

Many mammals have evolved to be social creatures. In humans, the ability to learn from others' experiences is essential to survival; and from an early age, individuals are surrounded by a social environment that helps them develop a variety of skills, such as walking, talking, and avoiding danger. Similarly, in rodents, behaviors, such as food preference, exploration of novel contexts, and social approach, can be learned through social interaction. Social encounters facilitate new learning and help modify preexisting memories throughout the lifespan of an organism. Moreover, social encounters can help buffer stress or the effects of negative memories, as well as extinguish maladaptive behaviors. Given the importance of such interactions, there has been increasing work studying social learning and applying its concepts in a wide range of fields, including psychotherapy and medical sociology. The process of social learning, including its neural and behavioral mechanisms, has also been a rapidly growing field of interest in neuroscience. However, the term "social learning" has been loosely applied to a variety of psychological phenomena, often without clear definition or delineations. Therefore, this review gives a definition for specific aspects of social learning, provides an overview of previous work at the circuit, systems, and behavioral levels, and finally, introduces new findings on the social modulation of learning. We contextualize such social processes in the brain both through the role of the hippocampus and its capacity to process "social engrams" as well as through the brainwide realization of social experiences. With the integration of new technologies, such as optogenetics, chemogenetics, and calcium imaging, manipulating social engrams will likely offer a novel therapeutic target to enhance the positive buffering effects of social experiences or to inhibit fear-inducing social stimuli in models of anxiety and post-traumatic stress disorder.
The association between cardio-respiratory fitness and incident depression: The Maastricht Study.
Journal of affective disorders, 2021

Moderate to vigorous physical activity (MVPA) can help to prevent depression, but identification of the most important psycho-biological pathways involved is unclear. The improvement of cardio-respiratory fitness (CRF) in response to MVPA can vary markedly, we therefore examined the association between CRF and the incidence of depressive symptoms.