rudyvdbrink/CitationDatabase huggingface dataset:
Tyrosine kinase inhibition increases functional parkin-Beclin-1 interaction and enhances amyloid clearance and cognitive performance.
EMBO molecular medicine, 2013

Tyrosine kinase inhibitors (TKIs) are effective therapies for leukaemia. Alzheimer is a neurodegenerative disease characterized by accumulation of β-amyloid (plaques) and hyper-phosphorylated Tau (tangles). Here we show that AD animals have high levels of insoluble parkin and decreased parkin-Beclin-1 interaction, while peripheral administration of TKIs, including Nilotinib and Bosutinib, increases soluble parkin leading to amyloid clearance and cognitive improvement. Blocking Beclin-1 expression with shRNA or parkin deletion prevents tyrosine kinase (TK) inhibition-induced amyloid clearance, suggesting that functional parkin-Beclin-1 interaction mediates amyloid degradation. Isolation of autophagic vacuoles (AVs) in AD mouse brain shows accumulation of parkin and amyloid, consistent with previous results in AD brains, while Bosutinib and Nilotinib increase parkin-Beclin-1 interaction and result in protein deposition in the lysosome. These data suggest that decreased parkin solubility impedes parkin-Beclin-1 interaction and amyloid clearance. We identified two FDA-approved anti-cancer drugs as potential treatment for AD.
Pilot study of sphenopalatine injection of onabotulinumtoxinA for the treatment of intractable chronic cluster headache.
Cephalalgia : an international journal of headache, 2016

The main object of this pilot study was to investigate the safety of administering onabotulinumtoxinA (BTA) towards the sphenopalatine ganglion (SPG) in intractable chronic cluster headache. Efficacy data were also collected to provide indication on whether future placebo-controlled studies should be performed.
Proteoglycan interactions with Sonic Hedgehog specify mitogenic responses.
Nature neuroscience, 2009

Sonic Hedgehog (Shh) has dual roles in vertebrate development, promoting progenitor cell proliferation and inducing tissue patterning. We found that the mitogenic and patterning functions of Shh can be uncoupled from one another. Using a genetic approach to selectively inhibit Shh-proteoglycan interactions in a mouse model, we found that binding of Shh to proteoglycans was required for proliferation of neural stem/precursor cells, but not for tissue patterning. Shh-proteoglycan interactions regulated both spatial and temporal features of Shh signaling. Proteoglycans localized Shh to specialized mitogenic niches and also acted at the single-cell level to regulate the duration of Shh signaling, thereby promoting a gene expression program that is important for cell division. Because activation of the Shh pathway is a feature of diverse human cancers, selective stimulation of proliferation by Shh-proteoglycan interactions may also figure prominently in neoplastic growth.
Relationship Between Cortical Thickness and Functional Activation in the Early Blind.
Cerebral cortex (New York, N.Y. : 1991), 2015

Early blindness results in both structural and functional changes of the brain. However, these changes have rarely been studied in relation to each other. We measured alterations in cortical thickness (CT) caused by early visual deprivation and their relationship with cortical activity. Structural and functional magnetic resonance imaging was performed in 12 early blind (EB) humans and 12 sighted controls (SC). Experimental conditions included one-back tasks for auditory localization and pitch identification, and a simple sound-detection task. Structural and functional data were analyzed in a whole-brain approach and within anatomically defined regions of interest in sensory areas of the spared (auditory) and deprived (visual) modalities. Functional activation during sound-localization or pitch-identification tasks correlated negatively with CT in occipital areas of EB (calcarine sulcus, lingual gyrus, superior and middle occipital gyri, and cuneus) and in nonprimary auditory areas of SC. These results suggest a link between CT and activation and demonstrate that the relationship between cortical structure and function may depend on early sensory experience, probably via selective pruning of exuberant connections. Activity-dependent effects of early sensory deprivation and long-term practice are superimposed on normal maturation and aging. Together these processes shape the relationship between brain structure and function over the lifespan.
Proximity extension assay testing reveals novel diagnostic biomarkers of atypical parkinsonian syndromes.
Journal of neurology, neurosurgery, and psychiatry, 2019

The high degree of clinical overlap between atypical parkinsonian syndromes (APS) and Parkinson's disease (PD) makes diagnosis challenging. We aimed to identify novel diagnostic protein biomarkers of APS using multiplex proximity extension assay (PEA) testing.
Effects of education on aging-related cortical thinning among cognitively normal individuals.
Neurology, 2015

We aimed to investigate the relationship between education and cortical thickness in cognitively normal individuals to determine whether education attenuated the association of advanced aging and cortical thinning.
Cortical cholinergic dysregulation as a long-term consequence of neonatal hypoglycemia.
Biochemistry and cell biology = Biochimie et biologie cellulaire, 2015

Neonatal hypoglycemia limits the glucose supply to cells, affecting the function of brain due to its high energy demand. This can cause long-term consequences in brain function, leading to memory and cognitive deficits. The present study evaluated the cholinergic functional regulation in cerebral cortex of one month old rats exposed to neonatal hypoglycemia to understand the long-term effects of early life stress. Receptor binding and gene expression studies were done in the cerebral cortex to analyze the changes in total muscarinicreceptors, muscarinic M1, M2, M3 receptors, and the enzymes involved in acetylcholine metabolism, cholineacetyl transferase and acetylcholine esterase. Neonatal hypoglycemia decreased total muscarinic receptors (p < 0.001) with reduced muscarinic M1, M2, and M3 receptor genes (p < 0.001) in one month old rats. The reduction in acetylcholine metabolism is indicated by the downregulated cholineacetyl transferase, upregulated acetylcholine esterase, and decreased vesicular acetylcholine transporter expression. These alterations in cholinergic function in one month old rat brain indicates the longterm consequences of neonatal hypoglycemia in cortical function, which can contribute to the onset of many disease conditions in later stages of life.
The dietary flavonoid isoliquiritigenin is a potent cytotoxin for human neuroblastoma cells.
Neuronal signaling, 2019

Neuroblastoma (NB) is the most common extracranial solid tumor of early childhood; it accounts for approximately 8-10% of all childhood cancers and is the most common cancer in children in the first year of life. Patients in the high-risk group have a poor prognosis, with relapses being common and often refractory to drug treatment in those that survive. Moreover, the drug treatment itself can lead to a range of long-term sequelae. Therefore, there is a critical need to identify new therapeutics for NB. Isoliquiritigenin (ISLQ) is a naturally-occurring, dietary chalcone-type flavonoid with a range of biological effects that depend on the cell type and context. ISLQ has potential as an anticancer agent. Here we show that ISLQ has potent cytotoxic effects on SK-N-BE(2) and IMR-32 human NB cells, which carry amplification of the
A Common Task Structure Links Together the Fate of Different Types of Memories.
Current biology : CB, 2020

Our memories frequently have features in common. For example, a learned sequence of words or actions can follow a common rule, which determines their serial order, despite being composed of very different events [1, 2]. This common abstract structure might link the fates of memories together. We tested this idea by creating different types of memory task: a sequence of words or actions that either did or did not have a common structure. Participants learned one of these memory tasks and then they learned another type of memory task 6 h later, either with or without the same structure. We then tested the newly formed memory's susceptibility to interference. We found that the newly formed memory was protected from interference when it shared a common structure with the earlier memory. Specifically, learning a sequence of words protected a subsequent sequence of actions learned hours later from interference, and conversely, learning a sequence of actions protected a subsequent sequence of words learned hours later from interference provided the sequences shared a common structure. Yet this protection of the newly formed memory came at a cost. The earlier memory had disrupted recall when it had the same rather than a different structure to the newly formed and protected memory. Thus, a common structure can determine what is retained (i.e., protected) and what is modified (i.e., disrupted). Our work reveals that a shared common structure links the fate of otherwise different types of memories together and identifies a novel mechanism for memory modification.
Human V6 Integrates Visual and Extra-Retinal Cues during Head-Induced Gaze Shifts.
iScience, 2018

A key question in vision research concerns how the brain compensates for self-induced eye and head movements to form the world-centered, spatiotopic representations we perceive. Although human V3A and V6 integrate eye movements with vision, it is unclear which areas integrate head motion signals with visual retinotopic representations, as fMRI typically prevents head movement executions. Here we examined whether human early visual cortex V3A and V6 integrate these signals. A previously introduced paradigm allowed participant head movement during trials, but stabilized the head during data acquisition utilizing the delay between blood-oxygen-level-dependent (BOLD) and neural signals. Visual stimuli simulated either a stable environment or one with arbitrary head-coupled visual motion. Importantly, both conditions were matched in retinal and head motion. Contrasts revealed differential responses in human V6. Given the lack of vestibular responses in primate V6, these results suggest multi-modal integration of visual with neck efference copy signals or proprioception in V6.
Microwave accelerated synthesis of isoxazole hydrazide inhibitors of the system xc- transporter: Initial homology model.
Bioorganic & medicinal chemistry letters, 2013

Microwave accelerated reaction system (MARS) technology provided a good method to obtain selective and open isoxazole ligands that bind to and inhibit the Sxc- antiporter. The MARS provided numerous advantages, including: shorter time, better yield and higher purity of the product. Of the newly synthesized series of isoxazoles the salicyl hydrazide 6 exhibited the highest level of inhibitory activity in the transport assay. A homology model has been developed to summarize the SAR results to date, and provide a working hypothesis for future studies.
Enhanced visual responses in the superior colliculus in an animal model of attention-deficit hyperactivity disorder and their suppression by D-amphetamine.
Neuroscience, 2014

Attention-deficit hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder characterized by overactivity, impulsiveness and attentional problems, including an increase in distractibility. A structure that is intimately linked with distractibility is the superior colliculus (SC), a midbrain sensory structure which plays a particular role in the production of eye and head movements. Although others have proposed the involvement of such diverse elements as the frontal cortex and forebrain noradrenaline in ADHD, given the role of the colliculus in distractibility and the increased distractibility in ADHD, we have proposed that distractibility in ADHD arises due to collicular sensory hyper-responsiveness. To further investigate this possibility, we recorded the extracellular activity (multi-unit (MUA) and local field potential (LFP)) in the superficial visual layers of the SC in an animal model of ADHD, the New Zealand genetically hypertensive (GH) rat, in response to wholefield light flashes. The MUA and LFP peak amplitude and summed activity within a one-second time window post-stimulus were both significantly greater in GH rats than in Wistar controls, across the full range of stimulus intensities. Given that baseline firing rate did not differ between the strains, this suggests that the signal-to-noise ratio is elevated in GH animals. D-Amphetamine reduced the peak amplitude and summed activity of the multi-unit response in Wistar animals. It also reduced the peak amplitude and summed activity of the multi-unit response in GH animals, at higher doses bringing it down to levels that were equivalent to those of Wistar animals at baseline. The present results provide convergent evidence that a collicular dysfunction (sensory hyper-responsiveness) is present in ADHD, and that it may underlie the enhanced distractibility. In addition, D-amphetamine - a widely used treatment in ADHD - may have one of its loci of therapeutic action at the level of the colliculus.
Genetics of CD33 in Alzheimer's disease and acute myeloid leukemia.
Human molecular genetics, 2015

The CD33 single-nucleotide polymorphism (SNP) rs3865444 has been associated with the risk of Alzheimer's disease (AD). Rs3865444 is in linkage disequilibrium with rs12459419 which has been associated with efficacy of an acute myeloid leukemia (AML) chemotherapeutic agent based on a CD33 antibody. We seek to evaluate the extent to which CD33 genetics in AD and AML can inform one another and advance human disease therapy. We have previously shown that these SNPs are associated with skipping of CD33 exon 2 in brain mRNA. Here, we report that these CD33 SNPs are associated with exon 2 skipping in leukocytes from AML patients and with a novel CD33 splice variant that retains CD33 intron 1. Each copy of the minor rs12459419T allele decreases prototypic full-length CD33 expression by ∼ 25% and decreases the AD odds ratio by ∼ 0.10. These results suggest that CD33 antagonists may be useful in reducing AD risk. CD33 inhibitors may include humanized CD33 antibodies such as lintuzumab which was safe but ineffective in AML clinical trials. Here, we report that lintuzumab downregulates cell-surface CD33 by 80% in phorbol-ester differentiated U937 cells, at concentrations as low as 10 ng/ml. Overall, we propose a model wherein a modest effect on RNA splicing is sufficient to mediate the CD33 association with AD risk and suggest the potential for an anti-CD33 antibody as an AD-relevant pharmacologic agent.
Globular adiponectin elicits neuroprotection by inhibiting NADPH oxidase-mediated oxidative damage in ischemic stroke.
Neuroscience, 2013

Recent studies indicate that adiponectin can attenuate cerebral ischemic lesions via its functional area located in the C-terminal globular domain, which is called globular adiponectin (gAD). However, the mechanisms underlying this action remain unclear. In this study, we investigated the antioxidant properties of gAD during cerebral ischemia. Adult male C57BL/6 mice received an intracerebral injection of gAD with or without tetrabromocinnamic acid (TBCA, a NADPH oxidase activator). Mice were subjected to middle cerebral artery occlusion (MCAO) after gAD injection. Infarct volume, neurological function, the activity of antioxidant enzymes (superoxide dismutase [SOD], catalase), the content of malondialdehyde (MDA), and the expression of Bax, Bcl-2, cleaved caspase-3 and NADPH oxidase 2 (NOX2) were examined at 24h after MCAO. Infarct volume was attenuated in gAD-transduced mice when compared with mice in the MCAO group, with significant improvement in neurological function. In addition, neuronal apoptosis was attenuated, along with the expression of Bax/Bcl-2 and cleaved caspase 3. Furthermore, the activities of SOD and catalase increased, and the content of MDA reduced. However, TBCA blocked the effect of gAD on cerebral protection and its antioxidant abilities. Taken together, these results demonstrate that the neuroprotective action of gAD may result from the promotion of antioxidant capacity by inhibiting the NOX2 signaling system.
Cytomegalovirus as an oncomodulatory agent in the progression of glioma.
Cancer letters, 2017

Glioblastoma multiforme (GBM) is the most aggressive neoplastic brain tumor in humans with a median survival of less than 2 years. It is therefore critical to understand the mechanism of glioma progression and to identify future targets for intervention. We investigate the mechanisms of cytomegalovirus as an oncomodulatory agent implicated in glioma progression, as well as immunosuppression. This review provides a comprehensive evaluation of recent investigative developments concerning the role of CMV in cellular processes during glioma growth. The manners in which CMV and its viral products interact with regulatory cellular signaling pathways in the host are of primary interest. Here, we examine some of the most significant oncomodulatory effects that CMV can confer in brain tumors, including the inhibition of apoptosis and promoting the growth of glioma stem cells, which are tightly linked to tumor survival and recurrence.
Inactivation of the medial preoptic area/anterior hypothalamus by lidocaine reduces male sexual behavior and sexual incentive motivation in male rats.
Neuroscience, 2008

Permanent bilateral lesions of the medial preoptic area anterior hypothalamus (MPOA/AH) produce a drastic inhibition of male sexual behavior in all species studied to date. The present experiment was designed to evaluate if temporal inactivation of the MPOA/AH by infusions of lidocaine also inhibits sexual behavior in male rats. This would allow us to rule out the possibility that the behavioral effects observed after damage of the MPOA/AH could be associated with plastic changes induced by the lesion in other brain regions. We also evaluated sexual incentive motivation in males after the infusion of lidocaine in a test in which copulation is not possible but where males maintain approach behavior to the estrous females despite repeated testing. The percentage of animals displaying mounts, intromissions and ejaculation was significantly reduced while mount and intromission latency were prolonged after infusion of lidocaine. No changes were observed in sexual behavior after infusion of lidocaine in animals with cannulae outside the MPOA/AH suggesting that the inhibitory effects are specific to this brain region. Sexual incentive motivation was also affected by administration of lidocaine. Males consistently showed a clear preference for the sexually receptive female except when infused with lidocaine. After the infusion of the compound a significant reduction in the time spent in the incentive zone of the stimulus female was observed. These results support the hypothesis that neurons of the MPOA/AH are involved in the control of male sexual motivation.
Psychiatric symptoms of noradrenergic dysfunction: a pathophysiological view.
Psychiatry and clinical neurosciences, 2014

What psychiatric symptoms are caused by central noradrenergic dysfunction? The hypothesis considered in this review is that noradrenergic dysfunction causes the abnormalities in arousal level observed in functional psychoses. In this review, the psychiatric symptoms of noradrenergic dysfunction were inferred pathophysiologically from the neuroscience literature. This inference was examined based on the literature on the biology of psychiatric disorders and psychotropics. Additionally, hypotheses were generated as to the cause of the noradrenergic dysfunction. The central noradrenaline system, like the peripheral system, mediates the alarm reaction during stress. Overactivity of the system increases the arousal level and amplifies the emotional reaction to stress, which could manifest as a cluster of symptoms, such as insomnia, anxiety, irritability, emotional instability and exaggerated fear or aggressiveness (hyperarousal symptoms). Underactivity of the system lowers the arousal level and attenuates the alarm reaction, which could result in hypersomnia and insensitivity to stress (hypoarousal symptoms). Clinical data support the hypothesis that, in functional psychoses, the noradrenergic dysfunction is in fact associated with the arousal symptoms described above. The anti-noradrenergic action of anxiolytics and antipsychotics can explain their sedative effects on the hyperarousal symptoms of these disorders. The results of animal experiments suggest that excessive stress can be a cause of long-term noradrenergic dysfunction.
Neurological Impact of Coronavirus Disease of 2019: Practical Considerations for the Neuroscience Community.
World neurosurgery, 2020

The coronavirus disease of 2019 (COVID-19), which is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has recently been designated a pandemic by the World Health Organization, affecting 2.7 million individuals globally as of April 25, 2020, with more than 187,000 deaths. An increasing body of evidence has supported central nervous system involvement.
An 8-Week Self-Administered At-Home Behavioral Skills-Based Virtual Reality Program for Chronic Low Back Pain: Double-Blind, Randomized, Placebo-Controlled Trial Conducted During COVID-19.
Journal of medical Internet research, 2021

Chronic low back pain is the most prevalent chronic pain condition worldwide and access to behavioral pain treatment is limited. Virtual reality (VR) is an immersive technology that may provide effective behavioral therapeutics for chronic pain.
Restless legs syndrome and its relationship with insomnia symptoms and daytime distress: epidemiological survey in Sweden.
Psychiatry and clinical neurosciences, 2008

To investigate prevalence estimates of restless legs syndrome (RLS) in relation to insomnia complaints and daytime distress a questionnaire was sent to a randomly selected sample of 1962 inhabitants of Uppsala, Sweden. The questionnaire included questions about sleep and daytime distress and the standardized four-question set for epidemiological settings recommended by the International RLS Study Group. A positive diagnosis of RLS was established in 18.8% of all responders. When the optional question about frequency was applied 5.8% reported frequent symptoms. Insomnia symptoms and daytime distress were significantly associated with the frequency of RLS symptoms.
A dual inhibition: microRNA-552 suppresses both transcription and translation of cytochrome P450 2E1.
Biochimica et biophysica acta, 2016

MicroRNAs (miRNAs) can direct post-transcriptional or transcriptional gene silencing. Here, we report that miR-552 is in the nucleus and cytosol and inhibits human cytochrome P450 (CYP) 2E1 expression at both transcriptional and post-transcriptional levels. MiR-552 via its non-seed sequence forms hybrids with a loop hairpin of the cruciform structure in CYP2E1 promoter region to inhibit SMARCE1 and RNA polymerase II binding to the promoter and CYP2E1 transcription. Expressing SMARCE1 reverses the inhibitory effects of miR-552 on CYP2E1 mRNA expression. MiR-552 with mutations in non-seed region losses its transcriptional, but retains its post-transcriptional repression to CYP2E1. In contrast, mutation in miR-552 seed sequence suppresses its inhibitory effects on CYP2E1 expression at protein, but not at mRNA, levels. Our results suggest that miR-552 is a miRNA with a dual inhibitory ability at transcriptional and post-transcriptional levels leading to an effective inhibition.