rudyvdbrink/CitationDatabase huggingface dataset:
Design of non-aggregating variants of Aβ peptide.
Biochemical and biophysical research communications, 2014

Self association of the amyloid-β (Aβ42) peptide into oligomers, high molecular weight forms, fibrils and ultimately neuritic plaques, has been correlated with progressive cognitive decline in Alzheimer's disease. Thus, insights into the drivers of the aggregation pathway have the capacity to significantly contribute to our understanding of disease mechanism. Functional assays and a three-dimensional crystal structure of the P3 amyloidogenic region 18-41 of Aβ were used to identify residues important in self-association and to design novel non-aggregating variants of the peptide. Biophysical studies (gel filtration, SDS-PAGE, dynamic light scattering, thioflavin T assay, and electron microscopy) demonstrate that in contrast to wild type Aβ these targeted mutations lose the ability to self-associate. Loss of aggregation also correlates with reduced neuronal toxicity. Our results highlight residues and regions of the Aβ peptide important for future targeting agents aimed at the amelioration of Alzheimer's disease.
Chronic bryostatin-1 rescues autistic and cognitive phenotypes in the fragile X mice.
Scientific reports, 2020

Fragile X syndrome (FXS), an X-chromosome linked intellectual disability, is the leading monogenetic cause of autism spectrum disorder (ASD), a neurodevelopmental condition that currently has no specific drug treatment. Building upon the demonstrated therapeutic effects on spatial memory of bryostatin-1, a relatively specific activator of protein kinase C (PKC)ε, (also of PKCα) on impaired synaptic plasticity/maturation and spatial learning and memory in FXS mice, we investigated whether bryostatin-1 might affect the autistic phenotypes and other behaviors, including open field activity, activities of daily living (nesting and marble burying), at the effective therapeutic dose for spatial memory deficits. Further evaluation included other non-spatial learning and memory tasks. Interestingly, a short period of treatment (5 weeks) only produced very limited or no therapeutic effects on the autistic and cognitive phenotypes in the Fmr1 KO2 mice, while a longer treatment (13 weeks) with the same dose of bryostatin-1 effectively rescued the autistic and non-spatial learning deficit cognitive phenotypes. It is possible that longer-term treatment would result in further improvement in these fragile X phenotypes. This effect is clearly different from other treatment strategies tested to date, in that the drug shows little acute effect, but strong long-term effects. It also shows no evidence of tolerance, which has been a problem with other drug classes (mGluR5 antagonists, GABA-A and -B agonists). The results strongly suggest that, at appropriate dosing and therapeutic period, chronic bryostatin-1 may have great therapeutic value for both ASD and FXS.
The supramammillary nucleus controls anxiety-like behavior; key role of GLP-1R.
Psychoneuroendocrinology, 2020

Anxiety disorders are among the most prevalent categories of mental illnesses. The gut-brain axis, along with gastrointestinally-derived neuropeptides, like glucagon-like peptide-1 (GLP-1), are emerging as potential key regulators of emotionality, including anxiety behavior. However, the neuroanatomical substrates from which GLP-1 exerts its anxiogenic effect remain poorly characterized. Here we focus on a relatively new candidate nucleus, the supramammillary nucleus (SuM), located just caudal to the lateral hypothalamus and ventral to the ventral tegmental area. Our focus on the SuM is supported by previous data showing expression of GLP-1R mRNA throughout the SuM and activation of the SuM during anxiety-inducing behaviors in rodents. Data show that chemogenetic activation of neurons in the SuM results in an anxiolytic response in male and female rats. In contrast, selective activation of SuM GLP-1R, by microinjection of a GLP-1R agonist exendin-4 into the SuM resulted in potent anxiety-like behavior, measured in both open field and elevated plus maze tests in male and female rats. This anxiogenic effect of GLP-1R activation persisted after high-fat diet exposure. Importantly, reduction of GLP-1R expression in the SuM, by AAV-shRNA GLP-1R knockdown, resulted in a clear anxiolytic response; an effect only observed in female rats. Our data identify a new neural substrate for GLP-1 control of anxiety-like behavior and indicate that the SuM GLP-1R are sufficient for anxiogenesis in both sexes, but necessary only in females.
Recent Updates and Advances in the Use of Glycated Albumin for the Diagnosis and Monitoring of Diabetes and Renal, Cerebro- and Cardio-Metabolic Diseases.
Journal of clinical medicine, 2020

Diabetes mellitus is a heterogeneous and dysmetabolic chronic disease in which the laboratory plays a fundamental role, from diagnosis to monitoring therapy and studying complications. Early diagnosis and good glycemic control should start as early as possible to delay and prevent metabolic and cardio-vascular complications secondary to this disease. Glycated hemoglobin is currently used as the reference parameter. The accuracy of the glycated hemoglobin dosage may be compromised in subjects suffering from chronic renal failure and terminal nephropathy, affected by the reduction in the survival of erythrocytes, with consequent decrease in the time available for glucose to attach to the hemoglobin. In the presence of these renal comorbidities as well as hemoglobinopathies and pregnancy, glycated hemoglobin is not reliable. In such conditions, dosage of glycated albumin can help. Glycated albumin is not only useful for short-term diagnosis and monitoring but predicts the risk of diabetes, even in the presence of euglycemia. This protein is modified in subjects who do not yet have a glycemic alteration but, as a predictive factor, heralds the risk of diabetic disease. This review summarizes the importance of glycated albumin as a biomarker for predicting and stratifying the cardiovascular risk linked to multiorgan metabolic alterations.
Archetypes and the 'Impoverished Genome' argument: updates from evolutionary genetics.
The Journal of analytical psychology, 2020

Throughout his career, Jung felt the psyche had 'ancestral layers' that contained elements of an individual's species history, and clinical experience has shown that this idea can be an aid to psychological healing and emotional well-being. Thus, some later thinkers have attempted to link such theoretical constructs to the genome, as Jung had little knowledge of genetics in his day. But in the early 2000s, genome studies suggested that the genome might contain too little content to be capable of encoding symbolic information. This opinion gave rise to an oft-repeated 'impoverished genome' argument, i.e. that the genome could not provide a significant contribution to the collective unconscious, prompting theorists to propose other sources for it, or to argue that it doesn't exist. Today, however, developments in evolutionary neurogenetics calls the impoverished genome argument into question for a number of independent reasons. These developments re-open the idea that the genome may be worth reconsidering as the biological substrate for the collective unconscious.
Enhanced dopamine D2 receptor function in hypothalamus and corpus striatum: their role in liver, plasma and in vitro hepatocyte ALDH regulation in ethanol treated rats.
Journal of biomedical science, 2008

Dopamine D(2) receptors are involved in ethanol self- administration behavior and also suggested to mediate the onset and offset of ethanol drinking. In the present study, we investigated dopamine (DA) content and Dopamine D(2) (DA D(2)) receptors in the hypothalamus and corpus striatum of ethanol treated rats and aldehyde dehydrogenase (ALDH) activity in the liver and plasma of ethanol treated rats and in vitro hepatocyte cultures. Hypothalamic and corpus striatal DA content decreased significantly (P < 0.05, P < 0.001 respectively) and homovanillic acid/dopamine (HVA/DA) ratio increased significantly (P < 0.001) in ethanol treated rats when compared to control. Scatchard analysis of [(3)H] YM-09151-2 binding to DA D(2) receptors in hypothalamus showed a significant increase (P < 0.001) in B(max) without any change in K(d) in ethanol treated rats compared to control. The K(d) of DA D(2) receptors significantly decreased (P < 0.05) in the corpus striatum of ethanol treated rats when compared to control. DA D(2) receptor affinity in the hypothalamus and corpus striatum of control and ethanol treated rats fitted to a single site model with unity as Hill slope value. The in vitro studies on hepatocyte cultures showed that 10(-5) M and 10(-7) M DA can reverse the increased ALDH activity in 10% ethanol treated cells to near control level. Sulpiride, an antagonist of DA D(2), reversed the effect of dopamine on 10% ethanol induced ALDH activity in hepatocytes. Our results showed a decreased dopamine concentration with enhanced DA D(2) receptors in the hypothalamus and corpus striatum of ethanol treated rats. Also, increased ALDH was observed in the plasma and liver of ethanol treated rats and in vitro hepatocyte cultures with 10% ethanol as a compensatory mechanism for increased aldehyde production due to increased dopamine metabolism. A decrease in dopamine concentration in major brain regions is coupled with an increase in ALDH activity in liver and plasma, which contributes to the tendency for alcoholism. Since the administration of 10(-5) M and 10(-7) M DA can reverse the increased ALDH activity in ethanol treated cells to near control level, this has therapeutic application to correct ethanol addicts from addiction due to allergic reaction observed in aldehyde accumulation.
Focal brainstem infarction in the adult rat.
Lab animal, 2021

Animal models are required to study the pathogenesis of brainstem ischemia and to develop new therapeutic approaches to promote functional recovery after ischemia in humans. Few models of brainstem ischemia are available, and they show great variability or cause early lethality. New, reliable animal models are therefore needed. By selectively ligating four points of the lower basilar artery, we developed a new focal basilar artery occlusion model that causes a localized brainstem ischemic lesion in female Sprague-Dawley rats. Analysis of ischemic lesion volume and neurological deficits over a period of 28 d showed that the rats present symptoms specific to this type of stroke while the ischemic lesion remains relatively unchanged over time. This procedure allows higher survival rates and extended observation periods compared with other models of brainstem ischemia. The procedure takes ~40 min, can be performed by researchers with basic surgical skills and does not require specialized surgical equipment. This protocol is highly reliable and will be useful to evaluate new therapeutic approaches to promote functional recovery in patients with brainstem ischemia.
Auditory cortex reflects goal-directed movement but is not necessary for behavioral adaptation in sound-cued reward tracking.
Journal of neurophysiology, 2020

Mounting evidence suggests that the role of sensory cortices in perceptual decision making goes beyond the mere representation of the discriminative stimuli and additionally involves the representation of nonsensory variables such as reward expectation. However, the relevance of these representations for behavior is not clear. To address this issue, we trained rats to discriminate sounds in a single-interval forced-choice task and then confronted the animals with unsignaled blockwise changes of reward probabilities. We found that unequal reward probabilities for the two choice options led to substantial shifts in response bias without concomitant reduction in stimulus discrimination. Although decisional biases were on average less extreme than required to maximize overall reinforcement, a model-based analysis revealed that rats managed to harvest >97% of rewards. Neurons in auditory cortex recorded during task performance weakly differentiated the discriminative stimuli but more strongly the subsequent goal-directed movement. Although 10-20% of units exhibited significantly different firing rates between task epochs with different response biases, control experiments showed this to result from inflated false positive rates due to unspecific temporal correlations of spiking activity rather than changing reinforcement contingencies. Transient pharmacological inactivation of auditory cortex reduced sound discriminability without affecting other measures of performance, whereas inactivation of medial prefrontal cortex affected both discriminability and bias. Together, these results suggest that auditory cortex activity only weakly reflects decisional variables during flexible updating of stimulus-response-outcome contingencies and does not play a crucial role in sound-cued adaptive behavior, beyond the representation of the discriminative stimuli.
Untangling Complexities of Glial-Neuronal Communications: Astroglial Metabolic Cascades Orchestrate Tonic Inhibition in the Thalamus.
Neuron, 2020

In this issue of Neuron, Kwak et al. describe novel astroglial pathway for synthesis of GABA, which is subsequently released through plasmalemmal Best1 channels to control neuronal excitability and tactile acuity through tonic inhibition of thalamic neurons.
Induction of BDNF Expression in Layer II/III and Layer V Neurons of the Motor Cortex Is Essential for Motor Learning.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2020

Motor learning depends on synaptic plasticity between corticostriatal projections and striatal medium spiny neurons. Retrograde tracing from the dorsolateral striatum reveals that both layer II/III and V neurons in the motor cortex express BDNF as a potential regulator of plasticity in corticostriatal projections in male and female mice. The number of these BDNF-expressing cortical neurons and levels of BDNF protein are highest in juvenile mice when adult motor patterns are shaped, while BDNF levels in the adult are low. When mice are trained by physical exercise in the adult, BDNF expression in motor cortex is reinduced, especially in layer II/III projection neurons. Reduced expression of cortical BDNF in 3-month-old mice results in impaired motor learning while space memory is preserved. These findings suggest that activity regulates BDNF expression differentially in layers II/III and V striatal afferents from motor cortex and that cortical BDNF is essential for motor learning.
Expression of p25, an aberrant cyclin-dependent kinase 5 activator, stimulates basal secretion in PC12 cells.
Molecules and cells, 2010

Although alterations in the functions of neurotransmitter systems have been implicated in the pathology of Alzheimer's disease (AD), the mechanisms that give rise to these alterations are not well understood. The amount of p25, an aberrant cleavage product of p35 that activates cyclin-dependent kinase 5 (Cdk5), is elevated in AD brains. The role of Cdk5 in neurotransmitter release has been well established. In this study, we examined whether p25 was linked to altered neurotransmitter release in AD. Transient or stable expression of p25 significantly increased basal secretion of human growth hormone (hGH) or neurotransmitter in PC12 cells. Expression of a p25 phosphorylation-deficient mutant, T138A, inhibited basal hGH secretion relative to the p25 wild type, suggesting the involvement of Thr138 phosphorylation in secretion. The expression and activity of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), a key protease in the generation of beta-amyloid, are increased in AD brains. Our previous studies indicated that overexpression of BACE1 enhanced basal secretion of hGH in PC12 cells. Transient coexpression of p25 and BACE1 further stimulated spontaneous basal secretion. These results indicate a novel role for p25 in the secretory pathway and suggest that elevated levels of p25 and BACE1 in AD brains may contribute to altered neurotransmitter pathology of AD through enhancing spontaneous basal secretion.
Non-pathological roles of microglial TREM2/DAP12: TREM2/DAP12 regulates the physiological functions of microglia from development to aging.
Neurochemistry international, 2020

Triggering receptor expressed on myeloid cells 2 (TREM2) forms a receptor complex with DNAX-activating protein of 12 kDa (DAP12) on the microglial plasma membrane. A wide variety of protein and non-protein ligands, including lipids and DNA, can bind to TREM2, inducing the activation of microglia via DAP12. Both Trem2 and Dap12 have been identified as causative genes for Nasu-Hakola disease, which causes presenile dementia in association with bone cysts. Furthermore, TREM2/DAP12 signaling represents an essential inducer of the activated microglial phenotype in neuronal diseases, including Alzheimer's disease. Therefore, most previous studies examining TREM2/DAP12 have focused on their roles in microglia under pathological conditions. However, a growing body of evidence has demonstrated the involvement of TREM2/DAP12 signaling in the regulation of physiological functions in microglia. Accordingly, by examining the importance of TREM2/DAP12 in the regulation of microglial activity during development, homeostasis, and aging in the brain, this review elucidates the roles played by this complex in the healthy brain.
Modulation of glutamatergic functional connectivity by a prototypical antipsychotic: Translational inference from a postsynaptic density immediate-early gene-based network analysis.
Behavioural brain research, 2021

Although extensively studied, the effect of antipsychotics is not completely understood at a network level. We tested the hypothesis that acute administration of haloperidol would modulate functional connectivity of brain regions relevant to schizophrenia pathophysiology. To assess putative changes in brain network properties and regional interactivity, we studied the expression of Homer1a, an Immediate Early Gene (IEG) demonstrated to be induced by antipsychotic administration and coding for a protein involved in glutamatergic synapses remodeling.
Young Neurons Tickle Memory during REM Sleep.
Neuron, 2020

Memory formation is a dynamic process and sleep is part of it. Consolidation of memories relies on finely orchestrated brain activities occurring during the post-learning sleep period. In this issue of Neuron, Kumar and colleagues provide evidence that the activity of adult-born hippocampal neurons during REM sleep is critical for the consolidation of episodic memory.
Mental disorders diagnosed in childhood and at-risk mental state in a help-seeking population.
Early intervention in psychiatry, 2013

Disorders usually first diagnosed in infancy, childhood or adolescence (DUFD-ICA) may have preceded the onset of psychosis by several years and share some co-morbidity with psychotic disorders, but only a few studies have investigated this aspect. We looked for past or current DUFD-ICA in a sample of first adult psychiatric service users assessed for the presence of an at-risk mental state with the Structured Interview for Psychosis-risk Syndromes (SIPS).
Enlarged perivascular spaces in multiple sclerosis on magnetic resonance imaging: a systematic review and meta-analysis.
Journal of neurology, 2020

Perivascular spaces can become detectable on magnetic resonance imaging (MRI) upon enlargement, referred to as enlarged perivascular spaces (EPVS) or Virchow-Robin spaces. EPVS have been linked to small vessel disease. Some studies have also indicated an association of EPVS to neuroinflammation and/or neurodegeneration. However, there is conflicting evidence with regards to their potential as a clinically relevant imaging biomarker in multiple sclerosis (MS).
Targeting the NCOA3-SP1-TERT axis for tumor growth in hepatocellular carcinoma.
Cell death & disease, 2020

Hepatocellular carcinoma (HCC) has a high mortality rate and lacks an effective therapeutic target. Elevated expression of human telomerase reverse transcriptase (TERT) is an important hallmark in cancers, but the mechanism by which TERT is activated differentially in cancers is poorly understood. Here, we have identified nuclear receptor coactivator-3 (NCOA3) as a new modulator of TERT expression and tumor growth in HCC. NACO3 specifically binds to the TERT promoter at the -234 to -144 region and transcriptionally activates TERT expression. NCOA3 promotes HCC cell growth and tumor progression in vitro and in vivo through upregulating the TERT signaling. Knockdown of NACO3 suppresses HCC cell viability and colony formation, whereas TERT overexpression rescues this suppression. NCOA3 interacts with and recruits SP1 binding on the TERT promoter. Knockdown of NCOA3 also inhibits the expression of the Wnt signaling-related genes but has no effect on the Notch signaling-targeting genes. Moreover, NCOA3 is positively correlated with TERT expression in HCC tumor tissues, and high expression of both NCOA3 and TERT predicts a poor prognosis in HCC patients. Our findings indicate that targeting the NCOA3-SP1-TERT signaling axis may benefit HCC patients.
Generation of interspecies mouse-rat chimeric embryos by embryonic stem (ES) cell microinjection.
STAR protocols, 2021

Interspecies chimerism is a useful tool to study interactions between cells of different genetic makeup in order to elucidate the mechanisms underlying non-cell-autonomous processes, including evolutionary events. However, generating interspecies chimeras with high efficiency and chimerism level remains challenging. Here, we describe a protocol for generating chimeras between mouse and rat. Donor embryonic stem cells of one species are microinjected into early embryos of the other species (recipient), which are implanted into host foster mothers of the recipient species. For complete details on the use and execution of this protocol, please refer to Stepien et al. (2020).
Reference noise method of removing powerline noise from recorded signals.
Journal of neuroscience methods, 2009

Powerline contamination of recorded signals represents a major source of noise in electrophysiology and impairs the use of recordings for research. In this article we present simple and effective method for cancelling 50 Hz (or 60 Hz) noise using a reference noise signal and average noise cycle subtraction. This method is capable of reliably removing not only the fundamental powerline frequency but also its harmonic frequencies. The efficiency of this method appears to be superior to other commonly used methods such as notch filtering or adaptive filtering. Our experience and results show that this method can be efficiently used with very low signal-to-noise ratios, while preserving original signal waveform.