A5087811455- Neuroscience and Neuropharmacology Research
- Neurotransmitter Receptor Influence on Behavior
- Drug Transport and Resistance Mechanisms
- Radiopharmaceutical Chemistry and Applications
- Receptor Mechanisms and Signaling
- Obsessive-Compulsive Spectrum Disorders
- Treatment of Major Depression
- Amino Acid Enzymes and Metabolism
- Tryptophan and brain disorders
- Traumatic Brain Injury and Neurovascular Disturbances
- Functional Brain Connectivity Studies
- Pharmacological Receptor Mechanisms and Effects
- Medical Imaging Techniques and Applications
- Cerebrospinal fluid and hydrocephalus
- Monoclonal and Polyclonal Antibodies Research
- Parkinson's Disease Mechanisms and Treatments
- Fetal and Pediatric Neurological Disorders
- HIV Research and Treatment
- Neuroscience and Neural Engineering
- Advanced X-ray and CT Imaging
- Cannabis and Cannabinoid Research
- Biochemical effects in animals
- Nerve injury and regeneration
- Ultrasound and Hyperthermia Applications
- RNA and protein synthesis mechanisms
Aarhus University
2020-2024
Rigshospitalet
2019-2024
Aarhus University Hospital
2021-2023
Copenhagen University Hospital
2019-2021
University of Copenhagen
2019-2020
Drug delivery to the central nervous system remains a major problem due biological barriers. The blood-brain-barrier can be bypassed by administering drugs intrathecally directly cerebrospinal fluid (CSF). glymphatic system, network of perivascular spaces promoting exchange between CSF and interstitial space, could utilized enhance convective drug from parenchyma. Glymphatic flow is highest during sleep anesthesia regimens that induce slow-wave sleep-like state. Here, using mass spectrometry...
The glymphatic system is a brain-wide waste drainage that promotes cerebrospinal fluid circulation through the brain to remove metabolites. Currently, most common methods for assessing function are ex vivo fluorescence microscopy of slices, macroscopic cortical imaging, and MRI. While all these have been crucial expanding our understanding system, new techniques required overcome their specific drawbacks. Here, we evaluate SPECT/CT imaging as tool assess in different anesthesia-induced...
Chemogenetic studies with the ligand clozapine N-oxide (CNO) are predicated upon assumption that CNO is devoid of actions at natural neuroreceptors. However, recent evidence shows may be converted back to (CLZ) in vivo, which could yield plasma concentrations sufficient occupy inter alia dopamine D2/3 and serotonin 5HT2A receptors living brain. To test this phenomenon, we measured striatal receptor occupancy [18F]fallypride PET ex vivo using [18F]MH.MZ. We found a dose-dependent effect on...
Parkinson's disease (PD) is characterized by Lewy body and neurite pathology associated with dopamine terminal dysfunction. Clinically, it motor slowing, rigidity, tremor. Postural instability pain are also features. Physical exercise benefits PD patients - possibly promoting neuroplasticity including synaptic regeneration.In a parkinsonian rat model, we test the hypotheses that exercise: (a) increases density reduces neuroinflammation (b) lowers nociceptive threshold increasing μ-opioid...
The N-methyl-D-aspartate receptor (NMDA-R) antagonist S-ketamine has been approved as a rapid-acting antidepressant for treatment-resistant depression (TRD). mechanisms have not fully elucidated; however, alterations of synaptic proteins and may play vital role. Here, we study the effect single subanaesthetic dose 15 mg/kg vs saline one hour after administration in Wistar Kyoto rat model on density vesicle glycoprotein 2A (SV2A) metabotropic glutamate 5 (mGluR5) using [3H]UCB-J [3H]MPEPγ...
Positron emission tomography (PET) is a molecular imaging technique that can be used to investigate the in vivo pharmacology of drugs. Initial preclinical evaluation PET tracers often conducted rodents due accessibility disease models as well economic considerations. Compared larger species, display higher expression and/or activity efflux transporters such P-glycoprotein (P-gp). Low brain uptake could, therefore, species-specific and not predictive for humans. We hypothesized better...
Diets high in sucrose and fat are becoming more prevalent the world over, accompanied by a raised prevalence of cardiovascular diseases, cancers, diabetes, obesity, metabolic syndrome. Clinical studies link unhealthy diets with development mental health disorders, particularly depression. Here, we investigate effects 12 days consumption administered as 2 L 25% solution daily for Göttingen minipigs on function brain receptors involved reward motivation, regulating feeding, pre- post-synaptic...
Abstract Objective Cocaine is a highly addictive psychostimulant that affects synaptic activity with structural and functional adaptations of neurons. The transmembrane vesicle glycoprotein 2A (SV2A) pre-synaptic vesicles commonly used to measure density, as novel approach the detection changes. We do not know if single dose cocaine suffices affect SV2A especially during adolescence when synapses undergo intense maturation. Here, we explored potential changes density in target brain areas...
The postsynaptic density (PSD) comprises numerous scaffolding proteins, receptors, and signaling molecules that coordinate synaptic transmission in the brain. Postsynaptic protein 95 (PSD-95) is a master scaffold within PSD one of its most abundant proteins therefore constitutes very attractive biomarker function pathological changes. Here, we exploit high-affinity inhibitor PSD-95, AVLX-144, as template for developing probes molecular imaging PSD. AVLX-144-based were labeled with...
The latest addition to the serotonin (5-HT) receptor family is 5-HT7 (5-HT7R). This has gained interest as a drug target due its involvement in various disorders such depression or schizophrenia. There currently no clinically validated positron emission tomography (PET) tracer for 5-HT7R available. But, (arylpiperazinyl-butyl)oxindole scaffold provides promising lead structure this purpose. Here, we synthesized 12 derivatives and vitro affinity screening identified two structures with...
The 5-HT7 receptor (5-HT7R) is involved in a broad range of physiological conditions and disorders. Currently, there no validated clinical positron emission tomography (PET) tracer available; however, we have recently developed promising 11C-labeled candidate. In this project, aimed to further extend our efforts develop an 18F-labeled derivative, coined [18F]ENL30. Fluorine-18 has several advantages over carbon-11 especially within the preclinical phase, where long half-life usually...
Abstract Major depressive disorder is one of the most prevalent mental health disorders, posing a global socioeconomic burden. Conventional antidepressant treatments have slow onset action, and 30% patients show no clinically significant treatment response. The recently approved fast‐acting S‐ketamine, an N‐methyl‐D‐aspartate receptor antagonist, provides new approach for treatment‐resistant patients. However, knowledge S‐ketamine's mechanism action still being established. Depressed human...
Abstract Dorsal striatal dopamine transmission engages the cortico-striato-thalamo-cortical (CSTC) circuit, which is implicated in many neuropsychiatric diseases, including obsessive-compulsive disorder (OCD). Yet it unknown if dorsal hyperactivity cause or consequence of changes elsewhere CSTC circuit. Classical pharmacological and neurotoxic manipulations other brain circuits suffer from various drawbacks related to off-target effects adaptive changes. Chemogenetics, on hand, enables a...
In preclinical positron emission tomography animal studies, continuous blood sampling is used to measure the time course of activity concentration in arterial blood. However, pigs have hypercoagulable that tends clot inside plastic tubes. We tested several tube materials and lengths use three-way connectors. validated set-ups for automated with without recirculation could run 90 minutes problematic clots any evidence emboli formation during necropsy.
Abstract Background: Positron Emission Tomography (PET) is a molecular imaging technique that can be used to investigate the in vivo pharmacology of drugs. Initial preclinical evaluation PET tracers often conducted rodents due accessibility disease models as well economic considerations. Compared larger species, display higher expression and/or activity efflux transporters such P-glycoprotein (P-gp). Low brain uptake could, therefore, species-specific and not predictive for humans. We...
Abstract Background Positron Emission Tomography (PET) is a molecular imaging technique that can be used to investigate the in vivo pharmacology of drugs. Initial preclinical evaluation PET tracers often conducted rodents due accessibility disease models as well economic considerations. Compared larger species, display higher expression and/or activity efflux transporters such P-glycoprotein (P-gp). Low brain uptake could, therefore, species-specific and not predictive for humans. We...
Abstract Background: Positron Emission Tomography (PET) is a molecular imaging technique that can be used to investigate the in vivo pharmacology of drugs. Initial preclinical evaluation PET tracers often conducted rodents due accessibility disease models as well economic considerations. Compared larger species, display higher expression and/or activity efflux transporters such P-glycoprotein (P-gp). Low brain uptake could, therefore, species-specific and not predictive for humans. We...