Electrical manipulation of Dopaminergic Neurons to modulate its survival

BERNARDI, ALEJANDRA; BAFFA-TRASCI, NATALIA; GERSHANIK, OSCAR; AVALE, MARIA ELENA; FERRARIO, JUAN ESTEBAN

Mar del Plata

Congreso; XXX SAN Annual meeting; 2015

Sociedad Argentina de Investigaciones en Neurociencias

Parkinson?s Disease (PD) is characterized by the selective death of nigral dopaminergic neurons, although the causes that determine their death still remain unknown. Several lines of evidence suggest that the peculiar electrical activity of these neurons plays a key role in determining their death or survival.Blocking electrical activity in vitro is able to induce their specific death, while pharmacological manipulations enhancing their electrical activity induce their survival, through an increase in intracellular Ca2+ levels. On the contrary, there are indications that an excess of Ca2+ signalling, as a consequence of electrical activity, results in a toxic condition for DA neurons.To put some light on this controversy, the purpose of this study is to manipulate the electrical conditions of DA cells with the use of DREADDs.We have reproduced an in vitro model of dopaminergic degeneration from embryonicmice, in which we have identified two subpopulations of DA neurons by their expression of Calbindine, a marker mostly expressed in DA neurons from VTA and not Substantia Nigra, and discriminate their response to protective agents, as nicotine. Finally, we transduced these cultures with stimulatory DREADD (M3) lentivirus preventing DA cell death when treated with CNO (Clozapine-N-Oxide) and artificial electrical stimulation was achieved.Further work is still necessary to demonstrate the role of electrical anipulation in death or survival of DA neurons.