Program in Neuroscience, University of Fribourg, Switzerland
Dr. Marco R. Celio
Institute of Histology and General Embryology
University of Fribourg
1700 FRIBOURG
SWITZERLAND
phone +41-26-300 8491
email Marco.Celio@unifr.ch
Website
Neurons expressing calcium binding proteins
Diseases of the nervous system - which account for many disabling maladies, such as brain ischaemia, epilepsy and neurodegenerative disorders - are precipitated by neuronal death. The final common pathway underlying nerve cell death in these diseases is believed to be an impaired intracellular homeostasis of calcium ions. Neurones are particularly vulnerable to elevations in the cytosolic concentration of calcium ions, owing to their possession of a multitude of voltage-, ligand- and second-messenger-gated ion channels. It is therefore not surprising that they are endowed with sophisticated means of guarding against gross changes in the intracellular activity of this cation; for this purpose, they are equipped with several intraneuronal systems which act in concert to buffer, sequester or remove the bulk of it. Potential, but controversial, contributors to this protective strategy are the intracellular calcium-binding proteins, of which parvalbumin is one of the best known representatives.
To address the function of parvalbumin within subpopulations of neurones, we are manipulating its concentration in vitro and in vivo. For in-vitro studies, various neuronal lines have been transfected with the cDNA for parvalbumin (and other calcium-binding proteins), and their susceptibility to death monitored. For in-vivo studies, parvalbumin-knock-out mice have been bred; the behavioural, physiological and cell-biological characteristics of this phenotype are currently being investigated (Beat Schwaller, group leader). Our aim is thus to tackle issues based on the hypothetical link between cellular calcium chelation and neuroprotection. Modulation of the levels of intracellular calcium-binding proteins may afford a means of rendering nerve cells less vulnerable to death in neurological disorders.
A second main research project at our institute concerns the composition of a peculiar extracellular matrix (the "perineuronal net") surrounding the parvalbumin-expressing nerve cells in the brain (Pierre-Alain Menoud, group leader).
Selected publications
Schwaller B., Durussel I., Jermann D., Herrmann B. & Cox J. Comparison of the Ca2+-binding properties of human recombinant calretinin-22k and calretinin J. Biol. Chem. 272: 29663-29671, 1997
Butt A.M., Ibrahim M. & Berry, M. Oligodendrocyte development and myelination in vivo in the anterior medullary velum of the rat brain. J. Neurocytol. 26: 327-338, 1997
Weisenhorn D.M.V., Celio M.R. & Rickmann M. The onset of parvalbumin expression in interneurons of the rat parietal cortex depends upon extrinsic factor(s). Europ. J. Neurosci. 10: 1027-1036, 1998