rudyvdbrink/CitationDatabase huggingface dataset:
Facilitation of axon regeneration by enhancing mitochondrial transport and rescuing energy deficits.
The Journal of cell biology, 2016

Although neuronal regeneration is a highly energy-demanding process, axonal mitochondrial transport progressively declines with maturation. Mature neurons typically fail to regenerate after injury, thus raising a fundamental question as to whether mitochondrial transport is necessary to meet enhanced metabolic requirements during regeneration. Here, we reveal that reduced mitochondrial motility and energy deficits in injured axons are intrinsic mechanisms controlling regrowth in mature neurons. Axotomy induces acute mitochondrial depolarization and ATP depletion in injured axons. Thus, mature neuron-associated increases in mitochondria-anchoring protein syntaphilin (SNPH) and decreases in mitochondrial transport cause local energy deficits. Strikingly, enhancing mitochondrial transport via genetic manipulation facilitates regenerative capacity by replenishing healthy mitochondria in injured axons, thereby rescuing energy deficits. An in vivo sciatic nerve crush study further shows that enhanced mitochondrial transport in snph knockout mice accelerates axon regeneration. Understanding deficits in mitochondrial trafficking and energy supply in injured axons of mature neurons benefits development of new strategies to stimulate axon regeneration.
Going retro: ancient viral origins of cognition.
Neuron, 2015

In this issue of Neuron, Zhang et al. (2015) provide the first crystal structure of a domain Arc. These results confirm prior computational approaches that suggested Arc, a master regulator of vertebrate synaptic plasticity, was "domesticated" from Ty3/Gypsy retrotransposons.
Controlling the Circadian Clock with High Temporal Resolution through Photodosing.
Journal of the American Chemical Society, 2019

Circadian clocks, biological timekeepers that are present in almost every cell of our body, are complex systems whose disruption is connected to various diseases. Controlling cellular clock function with high temporal resolution in an inducible manner would yield an innovative approach for the circadian rhythm regulation. In the present study, we present structure-guided incorporation of photoremovable protecting groups into a circadian clock modifier, longdaysin, which inhibits casein kinase I (CKI). Using photodeprotection by UV or visible light (400 nm) as the external stimulus, we have achieved quantitative and light-inducible control over the CKI activity accompanied by an accurate regulation of circadian period in cultured human cells and mouse tissues, as well as in living zebrafish. This research paves the way for the application of photodosing in achieving precise temporal control over the biological timing and opens the door for chronophotopharmacology to deeper understand the circadian clock system.
Contribution of pre-synaptic mechanisms to L-DOPA-induced dyskinesia.
Neuroscience, 2011

Positron emission tomography (PET) imaging studies have shown that peak-dose dyskinesia is associated to abnormally high levels of synaptic dopamine (DA) in the caudate-putamen of dyskinetic L-DOPA-treated patients. High striatal extracellular DA levels have also been found in dyskinetic 6-OHDA-lesioned rats as compared to non-dyskinetic ones, suggesting that extracellular DA levels may play a key role in the induction of dyskinesia. In this article we review the evidences pointing to the serotonin system as the primary cause for the abnormally high levels of L-DOPA-derived extracellular DA in Parkinson's disease, and we discuss the feasibility of a therapeutic approach targeting this system.
Cellular behavior controlled by bio-inspired and geometry-tunable nanohairs.
Nanoscale, 2017

A cicada wing has a biocidal feature of rupturing the membrane of cells, while the cactus spine can transmit a water drop to the stem of the plant. Both of these properties have evolved from their respective unique structures. Here, we endeavor to develop geometry-controllable nanohairs that mimic the cicada's wing-like vertical hairs and the cactus spine-like stooped hairs, and to quantitatively characterize the cell migration behavior of the hairy structures. It was found that the neuroblastoma cells are highly sensitive to the variation of surfaces: flat, vertical, and stooped nanohairs (100 nm diameter and 900 nm height). The cells on the vertical hairs showed significantly decreased proliferation. It was found that the behavior of cells cultured on stooped nanohairs is strongly influenced by the direction of the stooped pattern of hairs when we quantitatively measured the migration of cells on flat, vertical, and stooped structures. However, the cells on the flat structures showed random movement and the cells on the vertical nanohairs restricted the nanohair movement. Cells on the stooped structure showed higher forward migration preference compared to that of the other structures. Furthermore, we found that these cellular behaviors on the different patterns of nanohairs were affected by intracellular actin flament change. Consistent with these results, the vertical and stooped structures can facilitate the control of cell viability and guide directional migration for biomedical applications such as organogenesis.
Temporal cueing enhances neuronal and behavioral discrimination performance in rat whisker system.
Journal of neurophysiology, 2019

Since sensory systems operate with a finite quantity of processing resources, an animal would benefit from prioritizing processing of sensory stimuli within a time window that is expected to provide key information. This behavioral manifestation of such prioritization is known as attention. Here, we investigate attention with temporal cueing and its neuronal correlates in the rat primary vibrissal somatosensory (vS1) cortex. Rats were trained in a simple whisker vibration detection task. A vibration was presented at one of two spatial locations (left or right), sometimes after an unknown time interval and sometimes after receiving an auditory cue. The auditory cue provided temporal but not spatial information about the vibration. We found that for all rats ( n = 6), the auditory cue consistently enhanced detection of the vibration stimulus. Neuronal activity in vS1 cortex reflected the observed behavioral enhancement from temporal cueing with single units responded differentially to the whisker vibration stimulus when it was temporally predicted by the auditory cue, exhibiting an enhanced signal-to-noise ratio. Our findings indicate that rats are capable of prioritizing processing within a specified time window and provide evidence that the primary sensory cortex may participate in the temporal allocation of resources. NEW & NOTEWORTHY We demonstrate a novel paradigm of temporal cueing in rats. In a two-alternative whisker detection task, an auditory cue provided information about the timing of the stimulus but not the correct choice. In the presence of cue, detection was faster and more accurate, and neuronal activity from the primary somatosensory cortex revealed enhanced representation of vibrations. These results thus establish the rat as an alternative model organism to primates for studying temporal attention.
Formant-frequency discrimination of synthesized vowels in budgerigars (Melopsittacus undulatus) and humans.
The Journal of the Acoustical Society of America, 2017

Vowels are complex sounds with four to five spectral peaks known as formants. The frequencies of the two lowest formants, F1and F2, are sufficient for vowel discrimination. Behavioral studies show that many birds and mammals can discriminate vowels. However, few studies have quantified thresholds for formant-frequency discrimination. The present study examined formant-frequency discrimination in budgerigars (Melopsittacus undulatus) and humans using stimuli with one or two formants and a constant fundamental frequency of 200 Hz. Stimuli had spectral envelopes similar to natural speech and were presented with random level variation. Thresholds were estimated for frequency discrimination of F1, F2, and simultaneous F1 and F2 changes. The same two-down, one-up tracking procedure and single-interval, two-alternative task were used for both species. Formant-frequency discrimination thresholds were as sensitive in budgerigars as in humans and followed the same patterns across all conditions. Thresholds expressed as percent frequency difference were higher for F1 than for F2, and were unchanged between stimuli with one or two formants. Thresholds for simultaneous F1 and F2 changes indicated that discrimination was based on combined information from both formant regions. Results were consistent with previous human studies and show that budgerigars provide an exceptionally sensitive animal model of vowel feature discrimination.
Charting the territory: symptoms and functional assessment in children with progressive, non-curable conditions.
Archives of disease in childhood, 2014

Children with progressive, non-curable genetic, metabolic, or neurological conditions require specialised care to enhance their quality of life. Prevention and relief of physical symptoms for these children needs to begin at diagnosis, yet, little is known about their patterns of symptoms and functional abilities.
Toll-like Receptor 2 Facilitates Oxidative Damage-Induced Retinal Degeneration.
Cell reports, 2020

Retinal degeneration is a form of neurodegenerative disease and is the leading cause of vision loss globally. The Toll-like receptors (TLRs) are primary components of the innate immune system involved in signal transduction. Here we show that TLR2 induces complement factors C3 and CFB, the common and rate-limiting factors of the alternative pathway in both retinal pigment epithelial (RPE) cells and mononuclear phagocytes. Neutralization of TLR2 reduces opsonizing fragments of C3 in the outer retina and protects photoreceptor neurons from oxidative stress-induced degeneration. TLR2 deficiency also preserves tight junction expression and promotes RPE resistance to fragmentation. Finally, oxidative stress-induced formation of the terminal complement membrane attack complex and Iba1+ cell infiltration are strikingly inhibited in the TLR2-deficient retina. Our data directly implicate TLR2 as a mediator of retinal degeneration in response to oxidative stress and present TLR2 as a bridge between oxidative damage and complement-mediated retinal pathology.
Non-alcoholic fatty liver disease and cerebral small vessel disease in Korean cognitively normal individuals.
Scientific reports, 2019

We aimed to investigate the association between nonalcoholic fatty liver disease (NAFLD) and cerebral small vessel disease (CSVD) burden, especially according to the NAFLD severity. A total of 1,260 participants were included. The CSVD burden was assessed with white matter hyperintensities (WMH), lacunes, and microbleeds (MBs) on brain MRI. An ultrasound diagnosis of fatty liver was made based on standard criteria, and the Fibrosis-4 (FIB-4) index was used to classify participants with NAFLD with having a high-intermediate (FIB-4 ≥1.45) or low (FIB-4 < 1.45) probability of advanced fibrosis. A multivariable logistic regression analysis was used to assess the association between NAFLD and the presence of moderate to severe WMH, lacunes, and MBs. NAFLD had a significant association only with moderate to severe WMH (OR: 1.64, 95% CI: 1.10-2.42), even after controlling for cardiometabolic risk factors. A linear trend test showed a significant association between the severity of NAFLD fibrosis and the presence of moderate to severe WMH (p for trend <0.001). Our findings suggest that NAFLD, especially NAFLD with fibrosis, has a significant association with the presence of moderate to severe WMH in cognitively normal individuals, and NAFLD severity predicted more frequent moderate to severe WMH.
Astrocyte calcium signaling transforms cholinergic modulation to cortical plasticity in vivo.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011

Global brain state dynamics regulate plasticity in local cortical circuits, but the underlying cellular and molecular mechanisms are unclear. Here, we demonstrate that astrocyte Ca(2+) signaling provides a critical bridge between cholinergic activation, associated with attention and vigilance states, and somatosensory plasticity in mouse barrel cortex in vivo. We investigated first whether a combined stimulation of mouse whiskers and the nucleus basalis of Meynert (NBM), the principal source of cholinergic innervation to the cortex, leads to enhanced whisker-evoked local field potential. This plasticity is dependent on muscarinic acetylcholine receptors (mAChR) and N-methyl-d-aspartic acid receptors (NMDARs). During the induction of this synaptic plasticity, we find that astrocytic [Ca(2+)](i) is pronouncedly elevated, which is blocked by mAChR antagonists. The elevation of astrocytic [Ca(2+)](i) is crucial in this type of synaptic plasticity, as the plasticity could not be induced in inositol-1,4,5-trisphosphate receptor type 2 knock-out (IP(3)R2-KO) mice, in which astrocytic [Ca(2+)](i) surges are diminished. Moreover, NBM stimulation led to a significant increase in the extracellular concentration of the NMDAR coagonist d-serine in wild-type mice when compared to IP(3)R2-KO mice. Finally, plasticity in IP(3)R2-KO mice could be rescued by externally supplying d-serine. Our data present coherent lines of in vivo evidence for astrocytic involvement in cortical plasticity. These findings suggest an unexpected role of astrocytes as a gate for cholinergic plasticity in the cortex.
Environmental enrichment compensates for the effects of stress on disease progression in Tg2576 mice, an Alzheimer's disease model.
Journal of neurochemistry, 2011

Various environmental factors are known to influence the onset and progression of Alzheimer's disease (AD). Environmental enrichment was reported to improve cognitive performance in various Alzheimer's transgenic mice via an amyloid-related or unrelated mechanism. However, stress has been found to accelerate amyloid deposition and cognitive deficits in many AD models. The aim of this study was to determine whether environmental enrichment compensates for the effects of stress on disease progression in the Tg2576 mice, an established AD model. We housed Tg2576 mice under environmental enrichment, enrichment plus stress, stress, or control conditions at 3 months of age. In this study, we first report that environmental enrichment counteracts the effects of stress in terms of cognitive deficits, tau phosphorylation, neurogenesis, and neuronal proliferation during AD-like disease progression. These results strongly implicate the importance of environmental factors as a major modulator for the disease progression of AD.
Cardiovascular and behavioural responses to conditioned fear and restraint are not affected by retrograde lesions of A5 and C1 bulbospinal neurons.
Neuroscience, 2010

The aim of this study was to test a possible role of A5 neurons in the expression of the pressor and tachycardic responses to conditioned fear and restraint, two forms of psychological stress. Previous Fos studies have shown that the C1 adrenergic neurons and spinally projecting neurons in the vasopressor region of the rostral ventrolateral medulla are not activated by these two stressors, suggesting that these cardiovascular changes may be mediated by other premotor sympathetic (presympathetic) cell groups. The same studies also revealed that the A5 noradrenergic group was one of the main presympathetic cell groups to be activated in response to these two stressors. Thus, we hypothesized that the A5 group could mediate these cardiovascular responses. Conditioned fear and restraint were tested in rats implanted with radiotelemetric probes before and after retrograde lesion with the selective toxin anti-dopamine-beta-hydroxylase-saporin bilaterally injected in the spinal cord at T2-T3. Six animals were selected that had the most extensive loss of spinally projecting catecholaminergic neurons: A5 (81%-95%) and rostral C1 (59%-86%, which would include most C1 bulbospinal neurons). However, despite this major loss of noradrenergic and adrenergic presympathetic neurons, the magnitude of the cardiovascular response to conditioned fear and restraint was the same before and after the lesion. Associated behavioural changes were not affected either. The results indicate that A5 presympathetic neurons are not essential for the expression of the tachycardic and pressor responses to conditioned fear and restraint. They also confirm that C1 bulbospinal neurons are not involved in these responses. The presympathetic neurons driving the tachycardic and pressor responses to conditioned fear and restraint must be elsewhere.
Evaluation of a mobile team dedicated to behavioural disorders as recommended by the Alzheimer Cooperative Valuation in Europe joint action: observational cohort study.
European journal of neurology, 2016

Preventing behavioural crises appears to be crucial to promote quality of life of the patient-caregiver dyad, to reduce inappropriate hospitalizations and to delay institutionalization. The Alzheimer Cooperative Valuation in Europe promotes mobile care to prevent patients from severe behavioural and psychological symptoms in dementia. This study assessed the potential efficacy of a mobile team for Alzheimer's disease on hospitalization sparing and behavioural disorder reduction.
A new method for quantification and assessment of epileptiform activity in EEG with special reference to focal nocturnal epileptiform activity.
Brain topography, 2009

Quantification of epileptiform activity in EEG has been applied for decades. This has mainly been done by visual inspection of the recorded EEG. There have been many attempts using computers to quantify the activity, usually with moderate success. In a row of contexts, including Landau-Kleffner syndrome and the syndrome of epilepsy with continuous spike wave during slow sleep, the spike index (SI) has been applied to quantify [Symbol: see text]interictal nocturnal focal epileptiform activity', which is suggested as a general term for the epileptiform activity enhanced by sleep. However, the SI has been implemented differently by different authors and has usually not been well described and never properly defined. This study suggests a definition of SI that gives a semiautomatic and relatively robust algorithm for assessment. The method employs spike detection by means of template matching of the current source density estimate. The percentage of time within an epoch with interspike interval (ISI) below a given limit, usually 3 s, is returned as the SI. This is calculated during daytime and in non-REM sleep. The standard epoch length is 10 min. The parameter selection is discussed in the context of the influence of spikes and bursts on cognition. The described method gives reproducible results in routine use, gives clinical valuable information, and is easily implemented in a clinical setting. There is only a minor added workload for the electroencephalographer.
Changes in plasma concentration of taurine in stroke.
Neuroscience letters, 2011

Taurine is critical for proper brain functioning. Increase in plasma taurine concentration has already been shown in many diseases [1,2,5,10,12,14,17,22,25,47]. The plasma concentrations of taurine in 60 patients, suffering from stroke, were compared with that of 54 healthy volunteers. The plasma samples of the patients were obtained three times in the first five days of hospitalization. A Student's t-test showed a significant difference (P<0.0001) between the plasma concentrations of taurine of the patients group (136.5±8.2mmol/L) and the control group (41.9±2.5mmol/L). In addition, a one-way repeated measures ANOVA test showed that the mean plasma concentration of taurine in the patients during the first five days of hospitalization declined significantly from 136.9±8.2mmol/L in the first day of hospitalization to 120.1±5.9mmol/L on the third day and 110.2±7.0mmol/L by the fifth day (P>0.05). The plasma concentration of taurine was increased in the patients with stroke probably because of brain tissue damage. Although, according to the result of the study, mean plasma taurine concentration in stroke patients declined during five days of hospitalization. Further studies are needed to introduce taurine as a biomarker of recovery in stroke.
Development of sensitivity to orthographic errors in children: An event-related potential study.
Neuroscience, 2017

To study the development of orthographic sensitivity during elementary school, we recorded event-related brain potentials (ERPs) from 2nd and 4th grade children who were exposed to line drawing of object or animals upon which the correctly or incorrectly spelled name was superimposed. Stimulus-locked ERPs showed a modulation of a frontocentral negativity between 200 and 500ms which was larger for the 4th grade children but did not show an effect of correctness of spelling. This effect was followed by a pronounced positive shift which was only seen in the 4th grade children and which showed a modulation of spelling correctness. This effect can be seen as an electrophysiological correlate of orthographic sensitivity and replicates earlier findings in adults. Moreover, response-locked ERPs triggered to the children's button presses indicating orthographic (in)-correctness showed a succession of waves including the frontocentral error-related negativity and a subsequent negativity with a more posterior distribution. This latter negativity was generally larger for the 4th grade children. Only for the 4th grade children, this negativity was smaller for the false alarm trials suggesting a conscious registration of the error in these children.
Do infants of breast-feeding mothers benefit from additional long-chain PUFA from fish oil? A 6-year follow-up.
The British journal of nutrition, 2020

Fish-oil supplements are marketed as enhancing intelligence and cognitive performance. However, empirical data concerning the utility of these products in healthy term infants are mixed, particularly with respect to lasting effects into childhood. We evaluated whether fish-oil supplementation during infancy leads to better neurocognitive/behavioural development at 6 years. We conducted a double-blind randomised controlled trial of supplementation with n-3 long-chain PUFA in 420 healthy term infants. Infants received either fish oil (containing at least 250 mg DHA and at least 60 mg EPA) or placebo (olive oil) daily from birth to 6 months of age. Neurodevelopmental follow-up was conducted at a mean age of 6 years (sd 7 months), whereby 335 children were assessed for language, executive functioning, global intelligence quotient and behaviour. No significant differences were observed between the groups for the main neurocognitive outcomes. However in parent-report questionnaire, fish-oil supplementation was associated with negative externalising (P = 0·035, d = 0·24) and oppositional/defiant behaviour (P = 0·006, d = 0·31), particularly in boys (P = 0·01, d = 0·45; P = 0·004, d = 0·40). Our results provide evidence that fish-oil supplementation to predominantly breast-fed infants confers no significant cognitive or behavioural benefit to children at 6 years.
Losing Weight after Menopause with Minimal Aerobic Training and Mediterranean Diet.
Nutrients, 2020

It is a common belief that menopausal women have greater difficulty losing weight. The aim of this study was to assess the efficacy of a Mediterranean diet (MD) to promote weight loss in postmenopausal women. All participants were prescribed a hypocaloric traditional MD, tailored to the individual. Subjects were asked not to begin any kind of physical activity. Body composition was measured at the beginning and after 8 weeks of treatment. In total, 89 women (age 52.8 ± 4.5 years, BMI 30.0 ± 5.2 kg/m