Drosophila model for parkinson’s disease: function, anatomy and screening with phytoterapics from Sardinian and Indian flora (Withania somnifera and Mucuna pruriens)

Parkinson’s disease (PD) is one of the most common neurodegenerative diseases characterized by the clinical triad: tremor, akinesia and rigidity as well as olfactory disturbances. The fruit fly Drosophila melanogaster is becoming a powerful model organism to study neurodegenerative diseases. PINK1 mutants display many important diagnostic symptoms of the disease such as akinetic motor behavior. We sought to use this system to explore, besides the motor, also the olfactory dysfunction, if any, in PINK1 mutants. In the present study, we describe for the first time, neurophysiological and neuroanatomical results concerning the olfactory function in PINK1 mutant flies. In this respect, electrophysiological responses to synthetic and natural volatiles (essential oils) were recorded from groups of PINK1 mutant adults at three different time points in their life cycle. In addition, the olfactory and the motor behavior (climbing activity) were recorded in the same age matched groups. We found that mutant adults showed a decrease in the olfactory response to several chemicals and essential oil volatiles. The results showed that the olfactory response as well as the locomotor behavior in mutant adults decreased even more as the flies aged. Immunohistological analysis of the antennal lobes (ALs) in these mutants revealed structural abnormalities, especially in the expression of Bruchpilot protein, a marker for synaptic active zones. Transmission electron microscopy on presynaptic active zones pointed out mitochondrial alteration in cholinergic neurons projecting to the ALs. The combination of electrophysiological and morphological results suggests that the altered synaptic organization may be due to a neurodegenerative process. The phytochemicals delivery by feeding PINK1 mutants with M. pruriens and W. somnifera had different effects in increasing lifespan and in enhancing both the defective olfactory and locomotor behavior. Our results indicate that this model can be used as a tool for understanding PD pathogensis and pathophysiology. These data help to explore the potential of using drosophila as a model for monitoring PD progression and developing new treatments.