rudyvdbrink/CitationDatabase huggingface dataset:
Non-epithelial stem cells and cortical interneuron production in the human ganglionic eminences.
Nature neuroscience, 2013

GABAergic cortical interneurons underlie the complexity of neural circuits and are particularly numerous and diverse in humans. In rodents, cortical interneurons originate in the subpallial ganglionic eminences, but their developmental origins in humans are controversial. We characterized the developing human ganglionic eminences and found that the subventricular zone (SVZ) expanded massively during the early second trimester, becoming densely populated with neural stem cells and intermediate progenitor cells. In contrast with the cortex, most stem cells in the ganglionic eminence SVZ did not maintain radial fibers or orientation. The medial ganglionic eminence exhibited unique patterns of progenitor cell organization and clustering, and markers revealed that the caudal ganglionic eminence generated a greater proportion of cortical interneurons in humans than in rodents. On the basis of labeling of newborn neurons in slice culture and mapping of proliferating interneuron progenitors, we conclude that the vast majority of human cortical interneurons are produced in the ganglionic eminences, including an enormous contribution from non-epithelial SVZ stem cells.
Synaptogenesis Stimulates a Proteasome-Mediated Ribosome Reduction in Axons.
Cell reports, 2019

Ribosomes and a subset of cellular mRNAs are trafficked into axons of developing neurons. The axonal localization of translational machinery allows new proteins to be rapidly and locally synthesized during axonal growth and pathfinding. However, in mature neurons, axonal ribosomes are significantly reduced or even absent. The mechanism that elicits this removal is currently unknown. Here, we demonstrate that synapse formation is the trigger for ribosome reduction in mature axons. In vivo analysis shows that axonal ribosome levels decrease in rat brain at a developmental stage coincident with synapse formation. Next, we observe in vitro that different synaptogenic inducers trigger an overall decrease of ribosomal proteins and rRNA in the axons of spinal motor neurons. We further observe that this process is dependent on the ubiquitin-proteasome system but not on autophagy. Together, these data identify synaptogenesis as the long missing biological trigger that leads to ribosome disappearance during axonal maturation.
SIRT1 Mediates Apelin-13 in Ameliorating Chronic Normobaric Hypoxia-induced Anxiety-like Behavior by Suppressing NF-κB Pathway in Mice Hippocampus.
Neuroscience, 2018

We previously showed that apelin-13 ameliorates chronic normobaric hypoxia (CNH)-induced anxiety-like behavior in mice, the mechanism, however, is not well known. This study aims to investigate whether SIRT1 is involved in the anxiolytic effect of apelin-13 in CNH-treated mice, and to illustrate the potential underlying mechanism. We showed that apelin-13 treatment reversed a decrease in SIRT1 and an increase in acetylated p65 (lysine 310) proteins' expression in hippocampus of CNH-treated mice, indicating that apelin-13 inhibited NF-κB signaling pathway by activating SIRT1. Behaviorally, apelin-13 ameliorated CNH-induced anxiety-like behavior, EX-527 blocked the beneficial effect of apelin-13, and the anxiogenic effect of CNH was attenuated by resveratrol pretreatment, suggesting that SIRT1 was involved in the effect of apelin-13 against CNH-induced anxiety-like behavior in mice. We also showed that resveratrol treatment decreased IL-1β, IL-6, TNF-ɑ, PCNA, Bcl-2, and acetyl-p65 levels, but increased Bax and caspase 3 levels in hippocampus, suggesting a suppressive effect of resveratrol on cellular neuroinflammation and proliferation while a promotive effect on apoptosis of microglia in hippocampus. Finally, blockade of NF-κB activity by PDTC diminished CNH-induced anxiety-like behavior, indicating that NF-κB was involved in CNH-induced anxiety-like behavior in mice. In conclusion, this study provides the first evidence that SIRT1 mediates the anxiolytic effect of apelin-13 in CNH-treated mice through the inhibition of NF-κB pathway. These results imply that dysfunction of the apelin-SIRT1-NF-κB axis in hippocampus represents a potential mechanism that results in the induction of neuroinflammation and reduction in neuroprotection, thus induces anxiety-like behavior in CNH-treated mice.
Electrophysiological determinants of the clinical severity of axonal peripheral neuropathy.
Muscle & nerve, 2019

Electrophysiological diagnosis of axonal peripheral neuropathy (PN) is based on the attenuated amplitudes of nerve conduction studies (NCS), or a reduced sural/radial amplitude ratio (SRAR). We aimed to identify the electrophysiological determinants of the clinical severity of PN.
Enabling nanomaterial, nanofabrication and cellular technologies for nanoneuromedicines.
Nanomedicine : nanotechnology, biology, and medicine, 2015

Nanoparticulate delivery systems represent an area of particular promise for nanoneuromedicines. They possess significant potential for desperately needed therapies designed to combat a range of disorders associated with aging. As such, the field was selected as the focus for the 2014 meeting of the American Society for Nanomedicine. Regenerative, protective, immune modulatory, anti-microbial and anti-inflammatory products, or imaging agents are readily encapsulated in or conjugated to nanoparticles and as such facilitate the delivery of drug payloads to specific action sites across the blood-brain barrier. Diagnostic imaging serves to precisely monitor disease onset and progression while neural stem cell replacement can regenerate damaged tissue through control of stem cell fates. These, taken together, can improve disease burden and limit systemic toxicities. Such enabling technologies serve to protect the nervous system against a broad range of degenerative, traumatic, metabolic, infectious and immune disorders. From the clinical editor: Nanoneuromedicine is a branch of nanomedicine that specifically looks at the nervous system. In the clinical setting, a fundamental hurdle in nervous system disorders is due to an inherent inability of nerve cells to regenerate after damage. Nanotechnology can offer new approaches to overcome these challenges. This review describes recent developments in nanomedicine delivery systems that would affect stem cell repair and regeneration in the nervous system.
Primary lateral sclerosis: predicting functional outcome.
Amyotrophic lateral sclerosis & frontotemporal degeneration, 2013

Our objective was to investigate functional outcome in primary lateral sclerosis (PLS). We followed a group of 24 patients with PLS. Clinical (ALSFRS), respiratory, and neurophysiological (electromyography and transcranial magnetic stimulation) evaluations were performed at entry and regularly over the follow-up period. The time taken for a greater than 10% decrease in ALSFRS compared to the first assessment was defined as the dichotomous outcome; prognostic factors were evaluated using the Cox proportional hazard model. Results demonstrated that the median age at symptom onset was 54 years (range 28-75 years). In 46% symptoms began in the lower limbs, in 21% in the upper limbs and in 33% in bulbar muscles. The median symptom duration at first visit was 3.1 years (range 0.9-11.7 years). At last follow-up the median disease duration was 9.9 years (range 4.2-17.6 years). The median follow-up time was 4.6 years (range 2.1-11 years). We excluded from final analysis three patients with positive family history. Older age at onset (p = 0.019) was related to more rapid functional impairment; gender, forced vital capacity, region of onset and neurophysiological changes did not predict outcome. In conclusion, age is the most critical prognostic factor for functional outcome in PLS.
Cortical laminar resting-state signal fluctuations scale with the hypercapnic blood oxygenation level-dependent response.
Human brain mapping, 2020

Calibrated functional magnetic resonance imaging can remove unwanted sources of signal variability in the blood oxygenation level-dependent (BOLD) response. This is achieved by scaling, using information from a perfusion-sensitive scan during a purely vascular challenge, typically induced by a gas manipulation or a breath-hold task. In this work, we seek for a validation of the use of the resting-state fluctuation amplitude (RSFA) as a scaling factor to remove vascular contributions from the BOLD response. Given the peculiarity of depth-dependent vascularization in gray matter, BOLD and vascular space occupancy (VASO) data were acquired at submillimeter resolution and averaged across cortical laminae. RSFA from the primary motor cortex was, thus, compared to the amplitude of hypercapnia-induced signal changes (tSD
Scaffold protein Lin7 family in membrane skeletal protein complex in mouse seminiferous tubules.
Histochemistry and cell biology, 2019

The membrane skeletal complex, protein 4.1G-membrane palmitoylated protein 6 (MPP6), is localized in spermatogonia and early spermatocytes of mouse seminiferous tubules. In this study, we investigated the Lin7 family of scaffolding proteins, which interact with MPP6. By immunohistochemistry, Lin7a and Lin7c were localized in germ cells, and Lin7c had especially strong staining in spermatogonia and early spermatocytes, characterized by staging of seminiferous tubules. By immunoelectron microscopy, Lin7 localization appeared under cell membranes in germ cells. The Lin7 staining pattern in seminiferous tubules was partially similar to that of 4.1G, cell adhesion molecule 1 (CADM1), and melanoma cell adhesion molecule (MCAM). Lin7-positive cells included type A spermatogonia, as revealed by double staining for Lin28a. Lin7 staining became weaker in MPP6-deficient mice by immunohistochemistry and western blotting, indicating that MPP6 transports and maintains Lin7 in germ cells. The histology of seminiferous tubules was unchanged in MPP6-deficient mice compared to that of wild-type mice. In cultured spermatogonial stem cells maintained with glial cell line-derived neurotropic factor (GDNF), Lin7 was clearly expressed and immunolocalized along cell membranes, especially at cell-cell junctions. Thus, Lin7 protein is expressed in germ cells, and Lin7, particularly Lin7c, is a useful marker for early spermatogenesis.
Sour Sensing from the Tongue to the Brain.
Cell, 2019

The ability to sense sour provides an important sensory signal to prevent the ingestion of unripe, spoiled, or fermented foods. Taste and somatosensory receptors in the oral cavity trigger aversive behaviors in response to acid stimuli. Here, we show that the ion channel Otopetrin-1, a proton-selective channel normally involved in the sensation of gravity in the vestibular system, is essential for sour sensing in the taste system. We demonstrate that knockout of Otop1 eliminates acid responses from sour-sensing taste receptor cells (TRCs). In addition, we show that mice engineered to express otopetrin-1 in sweet TRCs have sweet cells that also respond to sour stimuli. Next, we genetically identified the taste ganglion neurons mediating each of the five basic taste qualities and demonstrate that sour taste uses its own dedicated labeled line from TRCs in the tongue to finely tuned taste neurons in the brain to trigger aversive behaviors.
Episodic memory retrieval success is associated with rapid replay of episode content.
Nature neuroscience, 2020

Retrieval of everyday experiences is fundamental for informing our future decisions. The fine-grained neurophysiological mechanisms that support such memory retrieval are largely unknown. We studied participants who first experienced, without repetition, unique multicomponent 40-80-s episodes. One day later, they engaged in cued retrieval of these episodes while undergoing magnetoencephalography. By decoding individual episode elements, we found that trial-by-trial successful retrieval was supported by the sequential replay of episode elements, with a temporal compression factor of >60. The direction of replay supporting retrieval, either backward or forward, depended on whether the task goal was to retrieve elements of an episode that followed or preceded, respectively, a retrieval cue. This sequential replay was weaker in very-high-performing participants, in whom instead we found evidence for simultaneous clustered reactivation. Our results demonstrate that memory-mediated decisions are supported by a rapid replay mechanism that can flexibly shift in direction in response to task goals.
Does menopause affect the epilepsy?
Seizure, 2008

Hormonal fluctuations in the menstrual cycle have been shown to have an impact on the epilepsy in women with catamenial epilepsy. The epilepsy frequency is higher in the elderly, and this part of the population is steadily increasing. It is therefore of interest whether the hormonal changes in the menopausal transition affects the epilepsy. The perimenopause is associated with hormonal fluctuations and may worsen the epilepsy in women with catamenial epilepsy. It has been suggested that seizures may improve after menopause, particularly in the women with catamenial epilepsy. There is still however, limited data on the effects of menopause on the epilepsy. Prospective studies imply a long time span, and research in this field is scarce. More research on the relationship between hormonal fluctuations and seizures may enable us to predict the effect on the epilepsy. Special awareness should be given to a woman with epilepsy in the menopausal transition.
Right hemisphere occipital rTMS impairs working memory in visualizers but not in verbalizers.
Scientific reports, 2019

Distinguishing between verbal and visual working memory processes is complicated by the fact that the strategy used is hard to control or even assess. Many stimuli used in working memory tasks can be processed via verbal or visual coding, such as the digits in the digit span backwards task (DSB). The present study used repetitive transcranial magnetic stimulation (rTMS) to examine the use of visual processing strategies in the DSB. A total of 47 German university students took part in the study, 23 spontaneously using a verbal processing strategy and 24 using a visual strategy. After rTMS to the right occipital cortex, visualizers showed a significantly stronger mean performance decrease compared to verbalizers. The results indicate that the visual cortex is more critical for visualizers compared to verbalizers in the DSB task. Furthermore, the favored processing modality seems to be determined by the preference for a cognitive strategy rather than the presentation modality, and people are aware of the applied strategy. These findings provide insight into inter-individual differences in working memory processing and yield important implications for laboratory studies as well as clinical practice: the stimulus does not necessarily determine the processing and the participant can be aware of that.
Bipolar risk and mental imagery susceptibility in a representative sample of Chinese adults residing in the community.
The International journal of social psychiatry, 2016

We need to better understand the cognitive factors associated with risk for bipolar disorders. Recent research suggests that increased susceptibility to mental imagery may be one such factor. However, since this research was primarily conducted with Western students and at a single time-point, it is not known whether the relationship between imagery susceptibility and bipolar symptoms exists across cultures or within the general community, or whether this relationship remains stable over time.
Changes in the Neuronal Control of the Urinary Bladder in a Model of Radiation Cystitis.
The Journal of pharmacology and experimental therapeutics, 2018

Currently, we have assessed the neuronal control of the urinary bladder in radiation cystitis and whether interstitial cells contribute to the condition. Fourteen days after bladder irradiation (20 Gy), rats were sedated and the urinary bladder was cut into two sagittal halves where electrical field stimulation (EFS; 5-20 Hz) was applied on the pelvic nerve afferents or stretch (80 mN) on one-half of the bladder, while contractions were registered on the contralateral half of the bladder in the absence and presence of increasing doses of imatinib (1-10 mg/kg; inhibitor of c-kit-positive interstitial cells), atropine (1 mg/kg; to block muscarinic M
Can conditioned reinforcers and Variable-Ratio Schedules make food- and fluid control redundant? A comment on the NC3Rs Working Group's report.
Journal of neuroscience methods, 2012

This commentary challenges the conclusions of the NC3Rs Working Group's recent special report that food- or fluid control is sometimes necessary to conduct modern neuroscientific investigations in macaque monkeys (Prescott et al., 2010). Given the potential suffering of animals subjected to food- or fluid control, the decision to subject an animal to such practices should be taken hesitantly. That decision hinges on to which extent the animal is willing to be involved in the task. The authors have done a scientific literature search and express expert opinion, but fail to mention two techniques that may greatly influence the animals' motivation to participate in the task and thus reduce the need for food- or fluid control, namely (1) the use of conditioned reinforcers in addition to primary reinforcers; and (2) the use of Variable-Ratio Schedules rather than continuous reinforcement. An ethical and humane approach to animal experimentation suggests that all options should be explored and thoroughly investigated before resorting to methods potentially challenging the animals' welfare.
Local brain connectivity across development in autism spectrum disorder: A cross-sectional investigation.
Autism research : official journal of the International Society for Autism Research, 2016

There is a general consensus that autism spectrum disorder (ASD) is accompanied by alterations in brain connectivity. Much of the neuroimaging work has focused on assessing long-range connectivity disruptions in ASD. However, evidence from both animal models and postmortem examination of the human brain suggests that local connections may also be disrupted in individuals with the disorder. Here, we investigated how regional homogeneity (ReHo), a measure of similarity of a voxel's timeseries to its nearest neighbors, varies across age in individuals with ASD and typically developing (TD) individuals using a cross-sectional design. Resting-state fMRI data obtained from a publicly available database were analyzed to determine group differences in ReHo between three age cohorts: children, adolescents, and adults. In typical development, ReHo across the entire brain was higher in children than in adolescents and adults. In contrast, children with ASD exhibited marginally lower ReHo than TD children, while adolescents and adults with ASD exhibited similar levels of local connectivity as age-matched neurotypical individuals. During all developmental stages, individuals with ASD exhibited lower local connectivity in sensory processing brain regions and higher local connectivity in complex information processing regions. Further, higher local connectivity in ASD corresponded to more severe ASD symptomatology. These results demonstrate that local connectivity is disrupted in ASD across development, with the most pronounced differences occurring in childhood. Developmental changes in ReHo do not mirror findings from fMRI studies of long-range connectivity in ASD, pointing to a need for more nuanced accounts of brain connectivity alterations in the disorder.
Drug prescriptions of adults with adolescent depression in a community sample.
Pharmacoepidemiology and drug safety, 2012

The prescription drugs have, to our knowledge, not been much studied in epidemiological samples with long-term follow-up. Accordingly, our purpose was to analyze the use of prescription drugs in adults with adolescent depression.
Discovery of 4-ethoxy-7H-pyrrolo[2,3-d]pyrimidin-2-amines as potent, selective and orally bioavailable LRRK2 inhibitors.
Bioorganic & medicinal chemistry letters, 2018

Inhibition of LRRK2 kinase activity with small molecules has emerged as a potential novel therapeutic treatment for Parkinson's disease. Herein we disclose the discovery of a 4-ethoxy-7H-pyrrolo[2,3-d]pyrimidin-2-amine series as potent LRRK2 inhibitors identified through a kinase-focused set screening. Optimization of the physicochemical properties and kinase selectivity led to the discovery of compound 7, which exhibited potent in vitro inhibition of LRRK2 kinase activity, good physicochemical properties and kinase selectivity across the kinome. Moreover, compound 7 was able to penetrate into the CNS, and in vivo pharmacology studies revealed significant inhibition of Ser935 phosphorylation in the brain of both rats (30 and 100 mg/kg) and mice (45 mg/kg) following oral administration.
Bipolar cell reduction precedes retinal ganglion neuron loss in a complex 1 knockout mouse model.
Brain research, 2017

Inherited mitochondrial complex 1 deficiency causes Leber's hereditary Optic Neuropathy (LHON) and retinal ganglion cell (RGC) degeneration, and optic neuropathies are common in many inherited mitochondrial diseases. How mitochondrial defects pathomechanistically trigger optic neuropathy remains unclear. We observe that complex 1-deficient Ndufs4-/- mice present with acute vision loss around p30, and this vision loss is coincident with an 'inflammatory wave'. In order to understand what causes the inflammatory wave we explored retinal pathology that occurs from p20-p30. The results indicated that in the period p20-p30 in Ndufs4-/- retinas, there is: significant reduction in bipolar cells, RGC dendritic atrophy, reduced PSD95, increased oxidative stress as manifested by increased 4HNE, HO1 and Cuzn-SOD, increased mitochondrial biogenesis and increased apoptosis. These precede the major induction of 'inflammatory wave' at p30 shown previously, but occur earlier than frank RGC loss at p42. In general, complex 1 deficiency in retina triggers oxidative stress and mitochondrial respiratory dysfunction that causes death of the most sensitive cells, including bipolar cells and their synaptic contacts and amacrine cells in the early period, 20-24days. The early death of these cells is the likely precursor to the sharp rise in inflammatory molecules that occurs at day 30 and coincides with vision loss, and greatly precedes the death of RGCs that occurs at p42. These data suggest that metabolic antioxidant support of the most sensitive cells in the retina, or anti-inflammatory suppression of the consequences of their death, are both rational strategies for mitochondrial blinding disease.
Long-term effects of cariprazine exposure on dopamine receptor subtypes.
CNS spectrums, 2014

All clinically effective antipsychotics are known to act on the dopaminergic system, and previous studies have demonstrated that repeated treatment with antipsychotics produced region-specific changes in dopamine receptor levels. Cariprazine is a dopamine D₃ and D₂ receptor partial agonist with preferential binding to D₃ receptors. We examined the effects of chronic cariprazine administration on dopamine receptor levels.