A5074921206- Ion Transport and Channel Regulation
- Ion channel regulation and function
- Electrolyte and hormonal disorders
- Neuroinflammation and Neurodegeneration Mechanisms
- Neurogenesis and neuroplasticity mechanisms
- Mitochondrial Function and Pathology
- Connexins and lens biology
- Neonatal Respiratory Health Research
- Neuroscience and Neuropharmacology Research
- Barrier Structure and Function Studies
- Cerebrospinal fluid and hydrocephalus
- ATP Synthase and ATPases Research
- Aldose Reductase and Taurine
- Erythrocyte Function and Pathophysiology
- Prenatal Substance Exposure Effects
- Advanced MRI Techniques and Applications
- Neuroscience of respiration and sleep
- Fetal and Pediatric Neurological Disorders
- Caveolin-1 and cellular processes
- Atomic and Subatomic Physics Research
- Congenital heart defects research
- RNA regulation and disease
- Diabetic Foot Ulcer Assessment and Management
- Signaling Pathways in Disease
- Ion Channels and Receptors
University of Oslo
2016-2025
657 Oslo
2020
Nord University
2013
Yale University
2003-2005
Johns Hopkins University
2001-2005
Institute of Basic Medical Sciences of the Chinese Academy of Medical Sciences
2004
University of Washington
2001-2003
Sandvik (Norway)
2003
University of Campania "Luigi Vanvitelli"
2003
Johns Hopkins Medicine
2003
Membrane water transport is critically involved in brain volume homeostasis and the pathogenesis of edema. The cDNA encoding aquaporin-4 (AQP4) channel protein was recently isolated from rat brain. We used immunocytochemistry high-resolution immunogold electron microscopy to identify cells membrane domains that mediate flux through AQP4. AQP4 abundant glial bordering subarachnoidal space, ventricles, blood vessels. also osmosensory areas, including supraoptic nucleus subfornical organ....
The water channel AQP4 is concentrated in perivascular and subpial membrane domains of brain astrocytes. These membranes form the interface between neuropil extracerebral liquid spaces. anchored at these by its carboxyl terminus to α-syntrophin, an adapter protein associated with dystrophin. To test functions pool, we studied mice homozygous for targeted disruption gene encoding α-syntrophin (α- Syn −/− ). animals show a marked loss from but no decrease other domains, as judged quantitative...
The Aquaporin-4 (AQP4) water channel contributes to brain homeostasis in perivascular astrocyte endfeet where it is concentrated. We postulated that AQP4 tethered at this site by binding of the C terminus P SD95- D iscs large- Z O1 (PDZ) domain syntrophin, a component dystrophin protein complex. Chemical cross-linking and coimmunoprecipitations from demonstrated association with complex, including dystrophin, β-dystroglycan, syntrophin. expression was studied skeletal muscle mice lacking...
Regulatory volume decrease (RVD) is a key mechanism for control that serves to prevent detrimental swelling in response hypo-osmotic stress. The molecular basis of RVD not understood. Here we show complex containing aquaporin-4 (AQP4) and transient receptor potential vanilloid 4 (TRPV4) essential astrocytes. Astrocytes from AQP4-KO mice astrocytes treated with TRPV4 siRNA fail respond hypotonic stress by increased intracellular Ca 2+ RVD. Coimmunoprecipitation immunohistochemistry analyses...
Abstract Fibrotic scar tissue limits central nervous system regeneration in adult mammals. The extent of fibrotic generation and distribution stromal cells across different lesions the brain spinal cord has not been systematically investigated mice humans. Furthermore, it is unknown whether scar-forming have same origin throughout types lesions. In current study, we compared scarring human pathological corresponding mouse models penetrating non-penetrating injury, traumatic ischemic stroke,...
Recovery from neuronal activation requires rapid clearance of potassium ions (K + ) and restoration osmotic equilibrium. The predominant water channel protein in brain, aquaporin-4 (AQP4), is concentrated the astrocyte end-feet membranes adjacent to blood vessels neocortex cerebellum by association with α-syntrophin protein. Although AQP4 has been implicated pathogenesis brain edema, its functions normal physiology are uncertain. In this study, we used immunogold electron microscopy compare...
The δ2 glutamate receptors are prominently expressed in Purkinje cells and thought to play a key role the induction of cerebellar long-term depression. synaptic subsynaptic localization δ rat cortex was investigated with sensitive high-resolution immunogold procedures. After postembedding incubation an antibody raised C-terminal peptide δ2, high gold particle densities occurred all parallel fiber synapses cell dendritic spines, whereas other were consistently devoid labeling. Among types...
An abnormal accumulation of extracellular K + in the brain has been implicated generation seizures patients with mesial temporal lobe epilepsy (MTLE) and hippocampal sclerosis. Experimental studies have shown that clearance is compromised by removal perivascular pool water channel aquaporin 4 (AQP4), suggesting an efficient depends on a concomitant flux through astrocyte membranes. Therefore, we hypothesized loss AQP4 might be involved pathogenesis MTLE. Whereas Western blot analysis showed...
The formation of brain edema, commonly occurring as a potentially lethal complication acute hyponatremia, is delayed following knockout the water channel aquaporin-4 (AQP4). Here we show by high-resolution immunogold analysis blood-brain-barrier that AQP4 expressed in endothelial cells well perivascular membranes astrocyte endfeet. A selective removal alpha-syntrophin deletion delays buildup edema (assessed Diffusion-weighted MRI) intoxication, despite presence normal complement AQP4. This...
Aquaporin-4 (AQP4) is the predominant water channel in brain and selectively expressed astrocytes. Astrocytic endfoot membranes exhibit tenfold higher densities of AQP4 than non-endfoot membranes, making an excellent marker astrocyte polarization. Loss polarization known to compromise astrocytic function be associated with impaired K+ homeostasis. Here we investigate by a combination light electron microscopic immunocytochemistry whether amyloid deposition loss polarization, using as marker....
The aquaporin-4 (AQP4) pool in the perivascular astrocyte membranes has been shown to be critically involved formation and dissolution of brain edema. Cerebral edema is a major cause morbidity mortality stroke. It therefore essential know whether AQP4 up- or down-regulated after an ischemic insult, because such changes would determine time course formation. Here we demonstrate by quantitative immunogold cytochemistry that striatum neocortex show distinct patterns expression reperfusion phase...
Abstract Waste from the brain has been shown to be cleared via perivascular spaces through so-called glymphatic system. According this model cerebrospinal fluid (CSF) enters in of arteries, crosses astrocyte endfoot layer, flows parenchyma collecting waste that is subsequently drained along veins. Glymphatic clearance dependent on astrocytic aquaporin-4 (AQP4) water channels are highly enriched endfeet. Even though polarized expression AQP4 endfeet thought crucial importance for CSF influx,...
Abstract Brain water transport is poorly understood at the molecular level, and marked changes occur during brain development. As aquaporin‐4 (AQP4) channel protein abundant in brain, expression levels subcellular distribution of this were examined postnatal This study focused on cerebellum, which showed same pattern AQP4 development as rest brain. Semiquantitative immunoblotting revealed very low first week. A pronounced increase was noted second week, from 2% adult level day 7 (PN7) to 25%...
The brain contains an intrinsic vasopressin fiber system the function of which is unknown. It has been demonstrated recently that astrocytes express high levels a water channel, aquaporin-4 (AQP4). Because known to regulate aquaporin expression and translocation in kidney collecting ducts thereby control reabsorption, we hypothesized might serve similar brain. By recording optical signals acute cortical slice preparation showed evoked neuronal activity generates radial flux neocortex. rapid...
Aquaporins are a family of water channels found in animals, plants, and microorganisms. A subfamily aquaporins, the aquaglyceroporins, permeable for as well certain solutes such glycerol, lactate, urea. Here we show that brain contains two isoforms AQP9--an aquaglyceroporin with particularly broad substrate specificity--and more prevalent these is expressed mitochondria. The mitochondrial AQP9 isoform detected an approximately 25 kDa band immunoblots. This likely to correspond new mRNA...
Taurine is an abundant organic osmolyte with antioxidant and immunomodulatory properties. Its role in the pathogenesis of chronic liver disease unknown. The phenotype was studied taurine transporter knockout (taut-/-) mice. Hepatic levels were ~21, 15 6 mumol/g wet weight adult wild-type, heterozygous (taut+/-) homozygous mice, respectively. Immunoelectronmicroscopy revealed almost complete depletion Kupffer sinusoidal endothelial cells, but not parenchymal cells Compared wild-type mice...
Surface coatings of nanoparticles (NPs) are known to influence advantageous features NPs as well potential toxicity. Iron oxide (Fe3O4) applied for both medical diagnostics and targeted drug delivery. We investigated the cytotoxicity genotoxicity uncoated iron (U-Fe3O4) in comparison with oleate-coated (OC-Fe3O4) NPs. Testing was performed vitro human lymphoblastoid TK6 cells primary blood cells. For testing, relative growth activity, trypan blue exclusion, 3H-thymidine incorporation...
The aim of this study was to investigate the relationship between aquaporin (AQP) water channel expression and pathological features early untreated inflammatory bowel disease (IBD) in humans.Patients suspected have IBD on basis predefined symptoms, including abdominal pain, diarrhea, and/or blood stool for more than 10 days, were examined at local hospital. Colonoscopy with biopsies performed samples taken. Patients who did not meet diagnostic criteria displayed no evidence infection or...
Abstract Fibrotic scar tissue formation occurs in humans and mice. The fibrotic impairs regeneration functional recovery. However, the origin of scar-forming fibroblasts is unclear. Here, we show that stromal forming derive from two populations perivascular cells after spinal cord injury (SCI) adult mice both sexes. We anatomically transcriptionally identify cell as pericytes fibroblasts. Fibroblasts are enriched white gray matter regions cord, respectively. Both recruited response to SCI...
Short peptides are important as lead compounds and molecular probes in drug discovery chemical biology, but their well-known drawbacks, such high conformational flexibility, protease lability, poor bioavailability short half-lives vivo, have prevented potential from being fully realized. Side chain-to-side chain cyclization, e.g., by ring-closing olefin metathesis, known stapling, is one approach to increase the biological activity of that has shown promise when applied 310- α-helical...