A5019495161- Sleep and Wakefulness Research
- Sleep and related disorders
- Circadian rhythm and melatonin
- Neuroscience and Neuropharmacology Research
- Regulation of Appetite and Obesity
- Neuroinflammation and Neurodegeneration Mechanisms
- Adenosine and Purinergic Signaling
- interferon and immune responses
- Sphingolipid Metabolism and Signaling
- Neurotransmitter Receptor Influence on Behavior
- Influenza Virus Research Studies
- Epigenetics and DNA Methylation
- Neuroscience of respiration and sleep
- Receptor Mechanisms and Signaling
- Genetics and Neurodevelopmental Disorders
- Immune Cell Function and Interaction
- Restless Legs Syndrome Research
- Animal Nutrition and Physiology
- Adolescent and Pediatric Healthcare
- Memory and Neural Mechanisms
- Obstructive Sleep Apnea Research
- RNA Interference and Gene Delivery
- IoT-based Smart Home Systems
- Animal Behavior and Welfare Studies
- Enzyme Structure and Function
University of Copenhagen
2016-2025
Novo Nordisk Foundation
2023
Rigshospitalet
2009-2022
UCB Pharma (Belgium)
2022
Lundbeck (Italy)
2022
Copenhagen University Hospital
2005-2021
Glostrup Hospital
2011-2019
California Center for Sleep Disorders
2018
Oslo University Hospital
2016
Kennedy Center
2016
Species differences occur in the brain concentrations of drugs, but reasons for these are not yet apparent. This study was designed to compare uptake three radiolabeled P-glycoprotein (P-gp) substrates across species using positron emission tomography. Brain and brain-to-plasma ratios were compared; [<sup>11</sup>C]verapamil rats, guinea pigs, monkeys; [<sup>11</sup>C](<i>S</i>)-(2-methoxy-5-(5-trifluoromethyltetrazol-1-yl)-phenylmethylamino)-2(<i>S</i>)-phenylpiperidine (GR205171) monkeys,...
Autosomal dominant cerebellar ataxia, deafness and narcolepsy (ADCA-DN) is characterized by late onset (30-40 years old) sensory neuronal deafness, narcolepsy-cataplexy dementia. We performed exome sequencing in five individuals from three ADCA-DN kindreds identified DNMT1 as the only gene with mutations found all affected individuals. Sanger confirmed de novo mutation p.Ala570Val one family, showed co-segregation of p.Val606Phe p.Ala570Val, phenotype, two other kindreds. An additional...
Recent advances in the identification of susceptibility genes and environmental exposures provide broad support for a post-infectious autoimmune basis narcolepsy/hypocretin (orexin) deficiency. We genotyped loci associated with other inflammatory diseases 1,886 individuals hypocretin-deficient narcolepsy 10,421 controls, all European ancestry, using custom genotyping array (ImmunoChip). Three located outside Human Leukocyte Antigen (HLA) region on chromosome 6 were significantly disease...
To compare clinical, electrophysiologic, and biologic data in narcolepsy without cataplexy with low (≤ 110 pg/ml), intermediate (110-200 normal (> 200 pg/ml) concentrations of cerebrospinal fluid (CSF) hypocretin-1.University-based sleep clinics laboratories.Narcolepsy (n = 171) control patients 170), all available CSF hypocretin-1.Retrospective comparison receiver operating characteristics curve analysis. Patients were also recontacted to evaluate if they developed by survival analysis.The...
Narcolepsy Type 1 (NT1) is a neurological sleep disorder, characterized by the loss of hypocretin/orexin signaling in brain. Genetic, epidemiological and experimental data support hypothesis that NT1 T-cell-mediated autoimmune disease targeting hypocretin producing neurons. While autoreactive CD4+ T cells have been detected patients, CD8+ only examined to minor extent. Here we detect specific toward narcolepsy-relevant peptides presented primarily NT1-associated HLA types blood 20 patients...
Patients with narcolepsy carry CD4 + T cells that react to peptides from both the sleep-regulating neuropeptide hypocretin and a 2009 H1N1 influenza A protein.
Significance GHB is a natural brain metabolite of GABA, previously reported to be neuroprotective. However, the high-affinity binding site for has remained elusive almost 40 y. We here unveil CaMKIIα, highly important neuronal kinase, as long-sought-after target. Via specific interaction within central hub domain analogs act stabilize oligomer complex. This potentially explains pronounced neuroprotective effects in cultured neurons exposed chemical insult and mice ischemia. The postischemic...
Summary Narcolepsy with cataplexy is a rare disease an estimated prevalence of 0.02% in European populations. shares many features disorders, particular the lack awareness serious consequences for healthcare supply. Similar to other diseases, only few countries have registered narcolepsy cases databases International Classification Diseases or registries health authorities. A promising approach identify disease‐specific adverse effects and needs delivery field diseases establish distributed...
Abstract Individuals with narcolepsy suffer from abnormal sleep patterns due to loss of neurons that uniquely supply hypocretin (HCRT). Previous studies found associations the human leukocyte antigen (HLA)-DQ6 allele and T-cell receptor α (TRA) J24 gene segment also suggested in vitro-stimulated T cells can target HCRT. Here, we present evidence vivo expansion DQ6-HCRT tetramer + /TRAJ24 /CD4 DQ6 individuals without narcolepsy. We identify related TRAJ24 TCRαβ clonotypes encoded by identical...
To improve the understanding of complex biological processes underlying development non-alcoholic steatohepatitis (NASH), a multi-omics approach combining bulk RNA-sequencing based transcriptomics, quantitative proteomics and single-cell was used to characterize tissue biopsies from histologically validated diet-induced obese (DIO) NASH mice compared chow-fed controls. Bulk showed clear distinction between phenotypes good correspondence mRNA protein level regulations, apart specific...
Abstract In rodent models of type 2 diabetes (T2D), sustained remission hyperglycemia can be induced by a single intracerebroventricular (icv) injection fibroblast growth factor 1 (FGF1), and the mediobasal hypothalamus (MBH) was recently implicated as brain area responsible for this effect. To better understand cellular response to FGF1 in MBH, we sequenced >79,000 single-cell transcriptomes from diabetic Lep ob/ob mice obtained on Days 5 after icv either or vehicle. A wide range...
Chronic electroencephalography (EEG) is a widely used tool for monitoring cortical electrical activity in experimental animals. Although chronic implants allow high-quality, long-term recordings preclinical studies, the electrodes are foreign objects and might therefore be expected to induce local inflammatory response. We here analyzed effects of cranial electrode implantation on glymphatic fluid transport provoking structural changes meninges cerebral cortex male female mice....
Hypocretin (Hcrt), also known as orexin, neuropeptide signaling stabilizes sleep and wakefulness in all vertebrates. A lack of Hcrt causes the disorder narcolepsy, increased has been speculated to cause insomnia, but while pathways are relatively well-described, intracellular mechanisms that regulate its expression remain unclear. Here, we tested role microRNAs (miRNAs) regulating expression. We found miR-137, miR-637, miR-654-5p target human HCRT gene. miR-137 is evolutionarily conserved...