Carlotta Grumelli THE SYNAPTIC SPLIT OF SNAP-25: DIFFERENT ROLES IN GLUTAMATERGIC AND GABAERGIC NEURONS? Previous studies (Verderio et al., 2004; Frassoni et al., 2005) have demonstrated a different sensitivity of GABAergic and glutamatergic neurons to the action of Botulinum toxins A and E (BoNT/A and E); during my PhD period, I aimed at specifically addressing the reasons at the basis of the lower efficacy of BoNT/A or BoNT/E at GABAergic terminals. To clarify this issue, the penetration, the route of entry and the persistence of BoNTs in excitatory and inhibitory cultured hippocampal neurons have been investigated in detail. I demonstrated that the preferential action of BoNT/A at excitatory synapses does not result from either the absence of BoNT receptors in interneurons, which may lead to a defective toxin penetration, or a different route of entry in inhibitory neurons; I also showed that the variable efficiency of BoNT/A and BoNT/E on different type of neurons is not to be ascribed to a defective toxin persistence in GABAergic cells. Finally, I demonstrated that exogenous expression of SNAP-25 into inhibitory neurons makes GABAergic vesicle recycling sensitive to BoNT/A, thus suggesting the possibility that the amount of SNAP-25 and not the toxin penetration is at the basis of the different effects of the two neurotoxins at excitatory or inhibitory terminals. Exogenously expressed SNAP-25 might substitute a putative, endogenous SNARE, resistant to BoNT/A action, thus making the exocytosis at inhibitory terminals sensitive to BoNT/A. These putative SNAP-25 neuronal isoforms includes SNAP-29 and SNAP-47. To get insights into the possibility that these isoforms may support exocytosis in inhibitory neurons, in the last part of my PhD period, I analyzed the expression of different SNAP-25 isoforms in GABAergic and glutamatergic neurons.
|Titolo:||The synaptic split of snap-25: different roles in glutamatergic and gabaergic neurons|
|Supervisori e coordinatori interni:||PANERAI, ALBERTO EMILIO|
|Data di pubblicazione:||2008|
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
|Citazione:||The synaptic split of snap-25: different roles in glutamatergic and gabaergic neurons ; tutor: C. Verderio, M. Matteoli ; coordinatore: A.E. Panerai. - Milano : Università degli studi di Milano. DIPARTIMENTO DI FARMACOLOGIA, CHEMIOTERAPIA E TOSSICOLOGIA MEDICA, 2008. ((20. ciclo, Anno Accademico 2006/2007.|
|Appare nelle tipologie:||13 - Tesi di dottorato discussa entro ottobre 2010|