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

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

ONLINE

Congreso; SAIB - SAMIGE Joint meeting 2021 on line; 2021

Argentine Society for Biochemistry and Molecular Biology Research - Argentinean Society for General Microbiology

Ferroptosis is a recently discovered type of cell death that results from iron (Fe)‐dependent lipid peroxide accumulation andhas been proposed as one of the main mechanisms responsible for neuronal death in Parkinson´s disease (PD). In thisconnection, 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 displaylipid dyshomeostasis that results in triacylglycerol accumulation and exacerbated phospholipid hydrolysis. In this work, ourgoal was to characterize the brain lipid profile in an in vivo model of ferroptosis. For this purpose, C57BL/6 mice weresubjected to Fe overload by performing a four-doses scheme of intraperitoneal administration (Fe-saccharate -800 or 1332mg/kg- or vehicle). During treatment (16 days), animal welfare and locomotor activity were periodically evaluated. Aftersacrifice, biochemical parameters were determined in several organs (brain, liver and kidney). Motor skills were assessed byusing open field and footprint tests. Mice exposed to Fe overload (1332 mg/kg) showed a 60% diminution of total distancetraveled, associated with a greater thigmotaxis (20%; p