IN VIVO FERROPTOSIS INDUCES LIPID CACOSTASIS: IMPLICATIONS FOR NEURODEGENERATION ASSOCIATED WITH PARKINSON´S DISEASE

MANISCALCHI, A.; FUNK, M.I.; BENZI JUNCOS, O.N.; ALZA, N.P.; CONDE, M.; URANGA, R.; SALVADOR, G.

Congreso; SAIB-SAMIGE Joint meeting 2021; 2021

Ferroptosis is a recently discovered type of cell death that results from iron (Fe)‐dependent lipid peroxide accumulation and has been proposed as one of the main mechanisms responsible for neuronal death in Parkinson´s disease (PD). In this connection, Fe accumulation in several brain regions, and specifically in the substantia nigra has been reported in PD patients. We have previously demonstrated that dopaminergic neurons exposed to α-synuclein overexpression and Fe overload display lipid dyshomeostasis that results in triacylglycerol accumulation and exacerbated phospholipid hydrolysis. In this work, our goal was to characterize the brain lipid profile in an in vivo model of ferroptosis. For this purpose, C57BL/6 mice were subjected to Fe overload by performing a four-doses scheme of intraperitoneal administration (Fe-saccharate -800 or 1332 mg/kg- or vehicle). During treatment (16 days), animal welfare and locomotor activity were periodically evaluated. After sacrifice, biochemical parameters were determined in several organs (brain, liver and kidney). Motor skills were assessed by using open field and footprint tests. Mice exposed to Fe overload (1332 mg/kg) showed a 60% diminution of total distance traveled, associated with a greater thigmotaxis (20%; p