Implementation of an axotomy paradigm in Drosophila wings to study the role of FKBP2 in neurodegeneration

GALIGNIANA, MARIO; RAMOS HRYB ANA BELÉN; PAGANI, MARIO RAFAEL

Villa Carlos Paz

Congreso; Reunion Anual SAN 2019; 2019

Sociedad Argentina de Neurociencias

FKBP51 and FKBP52 are immunophilins that bind immunosuppressive drugs suchas FK506. FKBP51/52 are abundant in the nervous system, are not related toimmunosuppression and their function at the neuronal level is unclear. FK506protects and regenerates the nervous system upon several types of injuries.Recently, we found that FK506 promotes in vitro neurodifferentiation andregeneration of murine neurons in a FKBP52-dependent manner. However, mechanisms involved in this effect have not been elucidated and in vivo studies are necessary. Here, we implemented a model of axotomy in Drosophila wing toinvestigate the role of FKBP52 in neuronal degeneration. In this model, glial cells or neurons expressing fluorescent proteins can be easily visualized over time and changes after nerve injury can be recorded. Using this model, we observed that 2 dpa (days post axotomy) there is an increase in pigment spots in the veins, a sign of inflammatory processes. 7 dpa there is an increase in intensity and discontinuous fluorescence patterns in glia cells. Finally, 2 and 7 dpa, the L1 nerve thickness is reduced and there is a fluorescence discontinuity and reduction of glutamatergic axons. Toxicity studies showed that treatments with FK506 for 3 days at concentrations ranging from 0.01 μM to 1 mM do not alter the survival of adult flies. This model will allow us to examine the effect of FK506 in vivo and the underlying mechanisms of FKBP52 in nerve injury.