NR AWNM
AU Senatore,A.; Colleoni,S.; Corbelli,A.; Villa,A.; Forloni,G.; Gobbi,M.; Chiesa,R.
TI Analysis of synaptic dysfunction in a transgenic mouse model of inherited prion diseases
QU International Conference - Prion 2006: Strategies, advances and trends towards protection of society - 3.10.-6.10.2006, Torino, Italy, Lingotto Conference Centre - Poster sessions PA-49
PT Konferenz-Poster
AB Tg(PG14) mice express a mouse PrP homologue of a nine-octapeptide insertion associated with an inherited prion disease. These mice accumulate in their brains a PrPsc-like form of the mutant protein that is weakly protease-resistant and aggregated into small oligomers. As this form accumulates, Tg(PG14) mice develop a fatal neurological disorder characterized by dramatic atrophy of the cerebellum due to loss of synaptic endings in the molecular layer and massive apoptosis of granule neurons. Deletion of the proapoptotic gene Bax efficiently rescues cerebellar granule neurons, but does not prevent synaptic loss in the molecular layer and development of the clinical symptoms. Moreover, the activity of the calcium/calmodulin-dependent phosphatase calcineurin, which plays a pivotal role in regulating synaptic activity, is strikingly reduced in the cerebella of presymptomatic Tg(PG14) mice. These observations suggest that PG14 PrP causes neurological disease by disrupting the normal neuronal connectivity or function in the cerebellum. To characterize the synaptic dysfunction in the cerebellum of Tg(PG14) mice, we are carrying out morphological, functional and biochemical investigations in purified synaptosomal fractions. Specific methods have been setup to measure calcium-dependent neurotransmitters release, and investigate the functionality of the phosphorylation-dependent mechanisms governing the exo-endocytotic cycle of synaptic vesicles.
AD A. Senatore, R. Chiesa: Dulbecco Telethon Institute and Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy; S. Colleoni, G. Forloni, M. Gobbi: Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy; A. Corbelli, A. Villa: Microscopy and Image Analysis Consortium, Monza, Italy. E-mail: senatore@marionegri.it
SP englisch
PO Italien