Neuroprotective effects of creatine against rotenone induced neurotoxicity and mitochondrial dysfunctions in Drosophila melanogaster

Recent studies have shown that dietary creatine (Cr)
supplementation has beneficial effects in models of acute/
chronic neurodegeneration, which are ascribed due to the
bioenergetic, antiapoptotic, antiexcitotoxic and antioxidant
properties. In the present study, we have attempted to
obtain insights into the neuroprotective effects of Cr in a
Drosophila model. The primary objective was to understand
if Cr offers protection against Rotenone induced
neurotoxic effects and basis of its neuroprotection. D.
melanogaster (Oregon K, adults) exposed to Cr (2, 5,
10 mM, diet) for 7 days showed no mortality, while the
levels of lipid peroxidation were diminished (10
40%) in
whole body homogenates. Further, we investigated if Cr
can protect against Rotenone (ROT) induced oxidative
stress, locomotor deficits and lethality. While ROT,
(500 mM) caused significant mortality (95%), co-exposure
with Cr offered robust protection against ROT-induced
lethality and locomotor deficits (by negative geotaxis).
While Cr alone had no effect on fly behavior, it markedly
(
50%) improved the performance of ROT flies. In a
satellite study, adult flies exposed to paraquat per se
(40 mM) showed significant mortality (95%, 72 h), while
Cr treated flies (10 mM) exhibited higher survival rate
(50%, 72 h) suggesting significant development of resistance.
Our results demonstrate the potential neuroprotective
effects of Cr in Drosophila, which are consistent with
the hypothesis that Cr possesses significant beneficial
effects against neurodegeneration.