A5071764021- Receptor Mechanisms and Signaling
- Neuropeptides and Animal Physiology
- Mitochondrial Function and Pathology
- Cerebral Venous Sinus Thrombosis
- Neurosurgical Procedures and Complications
- Regulation of Appetite and Obesity
- Cerebrospinal fluid and hydrocephalus
- Intracerebral and Subarachnoid Hemorrhage Research
- Traumatic Brain Injury and Neurovascular Disturbances
- Genetic Neurodegenerative Diseases
- Barrier Structure and Function Studies
- Advanced Proteomics Techniques and Applications
- Glaucoma and retinal disorders
- Genetic and Kidney Cyst Diseases
- Neuroscience of respiration and sleep
- Neurobiology and Insect Physiology Research
- Protein Degradation and Inhibitors
- Autophagy in Disease and Therapy
- Adipose Tissue and Metabolism
- Sleep and Wakefulness Research
- Infant Nutrition and Health
- Coenzyme Q10 studies and effects
- Congenital heart defects research
- Ubiquitin and proteasome pathways
- Fatty Acid Research and Health
University of Copenhagen
2017-2025
Copenhagen University Hospital
2017-2020
Rigshospitalet
2017-2020
Icahn School of Medicine at Mount Sinai
2013-2016
Albert Einstein College of Medicine
2010-2014
Yeshiva University
2013
Abstract Background Idiopathic intracranial hypertension (IIH) is a syndrome exhibiting elevated pressure (ICP), visual disturbances, and severe headache. IIH primarily affects young obese women, though it can occur in individuals of any age, BMI, sex. characterized by systemic metabolic dysregulation with profile increased androgen hormones. However, the contribution obesity/hormonal perturbations to cerebrospinal fluid (CSF) dynamics remains unresolved. Methods We employed female Zucker...
Significance The mechanism by which vertebrate animals control their body weight is a complex process involving variety of molecules that regulate feeding and metabolism. Some these are neuropeptides bind to specific receptors in centers the brain. One most abundant peptides brain, LENSSPQAPARRLLPP (named BigLEN), has been proposed function as neuropeptide involved regulating weight, but receptor through this peptide acts had not identified. We screened candidate found one, G protein-coupled...
Abstract Background Elevated intracranial pressure (ICP) is observed in many neurological pathologies, e.g. hydrocephalus and stroke. This condition routinely relieved with neurosurgical approaches, since effective targeted pharmacological tools are still lacking. The carbonic anhydrase inhibitor, acetazolamide (AZE), may be employed to treat elevated ICP. However, its effectiveness questioned, location of action unresolved, tolerability low. Here, we determined the efficacy mode AZE rat ....
Abstract Background Idiopathic intracranial hypertension (IIH) is a condition characterized by increased pressure (ICP), impaired vision, and headache. Most cases of IIH occur in obese women childbearing age, though BMI, female sex do not encompass all aspects pathophysiology. Systemic metabolic dysregulation has been identified with profile androgen excess. However, the mechanistic coupling between obesity/hormonal perturbations cerebrospinal fluid dynamics remains unresolved . Methods...
Neuropeptides are produced from larger precursors by limited proteolysis, first endopeptidases and then carboxypeptidases. Major required for these cleavages include prohormone convertase (PC) 1/3 PC2. In this study, quantitative peptidomics analysis was used to characterize the specific role PC1/3 plays in process. Peptides isolated hypothalamus, amygdala, striatum of null mice were compared with those heterozygous wild-type mice. Extracts labeled stable isotopic tags fractionated HPLC,...
Abstract Cerebrospinal fluid (CSF) dynamics hold implications for neurological health. Despite its importance, accurate quantification of the CSF secretion rate remains a challenge due to methodological controversies and influence anesthesia. A novel technique is established determine in awake freely moving rats, quantified with three different methodologies. The higher rats than anesthetized latter demonstrating no requirement mechanical ventilation optimal quantification. ≈10‐fold lower...
ProSAAS is the precursor of a number peptides that have been proposed to function as neuropeptides. Because proSAAS mRNA highly expressed in arcuate nucleus hypothalamus, we examined cellular localization several proSAAS-derived mouse hypothalamus and found they generally colocalized with neuropeptide Y (NPY), but not α-melanocyte stimulating hormone. However, unlike proNPY mRNA, which upregulated by food deprivation mediobasal neither nor were significantly altered 1–2 days wild-type mice....
Abstract Background Dysregulation of brain fluid homeostasis associates with pathologies in which accumulation leads to elevated intracranial pressure. Surgical intervention remains standard care, since specific and efficient pharmacological treatment options are limited for disturbed homeostasis. Such lack therapeutic targets originates, part, from the incomplete map molecular mechanisms underlying cerebrospinal (CSF) secretion by choroid plexus. Methods The transcriptomic profile rat...
Several neuropeptide systems in the hypothalamus, including Y and agouti-related protein (AgRP), control food intake. Peptides derived from proSAAS, a precursor implicated regulation of body weight, also GPR171 is heterotrimeric guanine nucleotide-binding (G protein)-coupled receptor (GPCR) for BigLEN (b-LEN), peptide proSAAS. To facilitate studies exploring physiological role GPR171, we sought to identify small-molecule ligands this by performing virtual screen compound library interaction...
Cytosolic carboxypeptidase 1 (CCP1) is a metallopeptidase that removes C-terminal and side-chain glutamates from tubulin. The Purkinje cell degeneration (pcd) mouse lacks CCP1 due to mutation. Previously, elevated levels of peptides derived cytosolic mitochondrial proteins were found in adult pcd brain, raising the possibility functions degradation intracellular peptides. To test this hypothesis, we used quantitative peptidomics technique compare peptide wild-type mice, examining heart,...
ProSAAS is the precursor for some of most abundant peptides found in mouse brain and other tissues, including named SAAS, PEN, LEN. Both SAAS LEN are big little forms due to differential processing. Initial processing proSAAS mediated by furin (and/or furin-like enzymes) carboxypeptidase D, while smaller generated secretory granule prohormone convertases E. In hypothalamus, PEN colocalize with neuropeptide Y. present study, were detected hypothalamus but not cell bodies Y-expressing neurons....
Diseases of raised intracranial pressure (ICP) cause severe morbidity and mortality. Multiple drugs are utilised to lower ICP including acetazolamide topiramate. However, the evidence for their use is unclear. We aimed assess modulatory effects molecular at choroid plexus (CP)
ABSTRACT Background Idiopathic intracranial hypertension (IIH) is a condition characterized by increased pressure (ICP), impaired vision, and headache. Most cases of IIH occur in obese women childbearing age, though BMI, female sex do not encompass all aspects pathophysiology. Systemic metabolic dysregulation has been identified with profile androgen excess. However, the mechanistic coupling between obesity/hormonal perturbations cerebrospinal fluid dynamics remains unresolved. Methods...
Abstract Elevated intracranial pressure (ICP) is observed in many neurological pathologies, e.g. hydrocephalus and stroke. This condition routinely relieved with neurosurgical approaches, since effective targeted pharmacological tools are still lacking. The carbonic anhydrase inhibitor, acetazolamide (AZE), may be employed to treat elevated ICP. However, its effectiveness questioned, location of action unresolved, tolerability low. Here, we vivo ex approaches reveal the efficacy mode AZE rat...
Abstract Background Dysregulation of brain fluid homeostasis associates with pathologies in which accumulation leads to elevated intracranial pressure. Surgical intervention remains standard care, since specific and efficient pharmacological treatment options are limited for disturbed homeostasis. Such lack therapeutic targets originates, part, from the incomplete map molecular mechanisms underlying cerebrospinal (CSF) secretion by choroid plexus. Methods The transcriptomic profile rat...