The Bernstein Center Freiburg

Informal Seminar
Fabrizio Sitzia

Department of Anatomy, University of Bristol, UK

Investigation of alpha7 nicotinic receptor signalling in the CNS
Monday, January 18, 2010
12:00 h sharp
Library, first floor
BCCN Building
Hansastr. 9a
Alpha7 nicotinic receptors (alpha7 nAChR) are widely distributed throughout the CNS, particularly in the hippocampus and cortex. They are implicated in a wide range of neurological disorders including Alzheimer’s disease and schizophrenia. It has long been appreciated that activation of nicotinic receptors within the CNS can produce a variety of behavioural changes including improvements to cognitive function. Several lines of evidence indicate that pharmacological enhancement of alpha7 nAChRs function through selective alpha7-agonists could be a potential therapeutic route to combat disease-related cognitive deficits. Infact some of these molecules are reported to have entered clinical trials in man. A recent approach adopted to increase alpha7 nAChR activity is to identify selective positive allosteric modulators (PAMs). alpha7 PAMs have been divided into two classes: type I PAMs increase agonist potency with only subtle effects on kinetics, whereas type II agents produce additional dramatic effects on desensitization and deactivation. The data presented in this thesis provide pharmacological and mechanistic characterization of some selective alpha7 PAMs, including two novel alpha7 PAMs, both in transfected cell line and acute slices. Furthermore, it reports novel properties of PAMs with respect to their temperature- and voltage-dependence. Agonism of alpha7 nAChRs and their potential role in the modulation of the excitatory synaptic transmission were also investigated.
The talk is open to the public. Guests are cordially invited!