Laboratory for Molecular Neuroscience

Summary of activity

The Laboratory for Molecular Neuroscience investigates molecular mechanisms involved in the development of acute and chronic neurodegenerative disease, with a focus on the role of glutamate excitotoxicity. It aims at unravelling the molecular basis for cell death and endema development in stroke and other neurological conditions, and explores the pathophysiology of Alzheimer’s disease and temporal lobe epilepsy. Long terms goals are to identify new molecular targets for Neuroprotective strategies in stroke and other conditions involving glutamate excitotoxicity and to unravel the physiological and pathophysiological role of astrocyte endfeet.

  • Aquaporin-4 (AQP4): A molecular target for the treatment of brain edema?
  • Expression pattern and turnover of glutamate receptors
  • Molecular mechanisms underlying the generation of beta-amyloid in Alzheimer’s disease
  • Growth factors and Parkinson's disease
  • Development of laser microscopy imaging techniques
  • Digital Microscopy and Image Analysis
  • Perturbation of glutamate neurotransmission in human temporal epilepsy
  • Mechanisms underlying excitotoxicity and preferential vulnerability of CA1 cell The Brain's Synapses - Proteins and Vesicles regulate the information flux in the Central Nervous System

Contact information

Web-pages:
Laboratory for Molecular Neuroscience
Group home page
Water Imbalance Related Disorders
Glutamate Receptor Interacting Proteins as Novel Neuroprotective Targets

Address:
Centre for Molecular Biology and Neuroscience
Institute of Basic Medical Sciences,
University of Oslo
POB 1105 Blindern,
N-0317 Oslo, Norway

Street address:
Centre for Molecular Biology and Neuroscience
Institute of Basic Medical Sciences,
Domus Medica (Sognsvannsveien 9),
University of Oslo,
N-0317 Oslo, Norway

Fax: +47 22851488
Phone +47 22851528

Senior personnel

Prof. Ole P. Ottersen (head of laboratory)
Prof. em. Finn Mogens S. Haug
Prof. em. Kirsten Osen
Prof. Eric Rinvik
Guest professor: Peter Agre, Duke University, USA
Ass. prof. Svend Davanger
Senior researcher Reidun Torp
full list

Experimental tools

Immunocytochemistry:
Generation, purification, and testing of primary antibodies
Gold-, enzyme- and fluorescent labeling of sec­ondary anti­bodies
In situ hybridization
Light- and electron microscopy

Electron microscopy:
Transmission electron microscopy (TEM)
Freeze-substitution embedding
Ultracryotomy

Light microscopy:
Visual light microscopy
IR-DIC video microscopy
Fluorescence microscopy with cooled CCD camera, Ca2+ imaging
Cryostats, Vibratomes

Digital imaging:
On-line image-acquisition in wide field light- and electron microscopy
Networked image-storage, -processing, -analysis.
Semi-automated counting of particle density over organ­elles and membranes, data automatically aggregated and exported for graphical and statistical analysis
Video-cameras, standard and IR-sensitive
High-resolution, cooled, slow-scan CCD-cam­eras for fluorescence imaging
Image-combining computerized micros­copy
3D-imaging: see Laser-scan microscopy

Laserscan and multimode micros­copy (LSM laboratory):
Leica TCS SP scanner with three microscopes on vibration-free optical table
Confocal and multi-photon excitation modes. Mirror-coupled Titanium Sapphire laser for multi photon excitation mode, including un­caging
Co-ordinated imaging and electrophysiology of thick and thin specimens/single cells (upright fixed stage, respectively inverted, microscope)
Full complements of objectives, fluorescence filters for widefield mode, ports for CCD- and videocameras
Temperature-controlled perfusion system

Cell and tissue cultures:
Primary cell culture
Cell transfection
Dissociated neuronal cultures
Organotypic slice cultures

Key publications

  • Frydenlund DS, Bhardwaj A, Otsuka T, Mylonakou MN, Yasumura T, Davidson KG, Zeynalov E, Skare O, Laake P, Haug FM, Rash JE, Agre P, Ottersen OP, Amiry-Moghaddam M (2006) Temporary loss of perivascular aquaporin-4 in neocortex after transient middle cerebral artery occlusion in mice. Proc Natl Acad Sci USA, Sep 5;103(36):13532-6. Epub 2006 Aug 28.
  • Nagelhus EA, Mathiisen TM, Bateman AC, Haug FM, Ottersen OP, Grubb JH, Waheed A, Sly WS. (2005) Carbonic anhydrase XIV is enriched in specific membrane domains of retinal pigment epithelium, Muller cells, and astrocytes. Proc Natl Acad Sci USA. 2005 May 31;102(22):8030-5.
  • Ottersen OP. (2005) Neurobiology: sculpted by competition. Nature. 2005 Apr 21;434(7036):969.
  • Eid T, Lee TS, Thomas MJ, Amiry-Moghaddam M, Bjornsen LP, Spencer DD, Agre P, Ottersen OP, de Lanerolle NC. (2005)Loss of perivascular aquaporin 4 may underlie deficient water and K+ homeostasis in the human epileptogenic hippocampus. Proc Natl Acad Sci USA. 2005 Jan 25;102(4):1193-8. Epub 2005 Jan 18.
  • Amiry-Moghaddam M, Xue R, Haug FM, Neely JD, Bhardwaj A, Agre P, Adams ME, Froehner SC, Mori S, Ottersen OP (2004) Alpha-syntrophin deletion removes the perivascular but not endothelial pool of aquaporin-4 at the blood-brain barrier and delays the development of brain edema in an experimental model of acute hyponatremia. FASEB J. 18(3): 542-4.
  • Eid T, Thomas MJ, Spencer DD, Runden-Pran E, Lai JC, Malthankar GV, Kim JH, Danbolt NC, Ottersen OP, de Lanerolle NC (2004) Loss of glutamine synthetase in the human epileptogenic hippocampus: possible mechanism for raised extracellular glutamate in mesial temporal lobe epilepsy. Lancet; 63(9402):28-37.
  • Amiry-Moghaddam M, Williamson A, Palomba M, Eid T, de Lanerolle NC, Nagelhus, EA, Adams ME, Froehner SC, Agre P, Ottersen OP (2003) Delayed K+ clearance associated with aquaporin-4 mislocalization: phenotypic defects in brains of alpha-syntrophin-null mice. Proc Natl Acad Sci USA.; 100(23):13615-20.
  • Amiry-Moghaddam M, Ottersen OP (2003) The molecular basis of water transport in the brain. Nature Rev Neurosci. 4(12):991-1001.
  • Amiry-Moghaddam M, Otsuka T, Hurn PD, Traystman RJ, Haug FM, Froehner SC, Adams ME, Neely JD, Agre P, Ottersen OP, Bhardwaj A (2003) An alpha-syntrophin-dependent pool of AQP4 in astroglial end-feet confers bidirectional water flow between blood and brain. Proc Natl Acad Sci USA.;100(4):2106-11.
  • Ottersen OP, Helm PJ (2002) How hardwired is the brain? Nature 420(6917):751-2.