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

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

VIRTUAL

Congreso; SAIB-SAMIGE 2021,; 2021

SAIB-SAMIGE

in vivo Ferroptosis induces lipid cacostasis: implications for neurodegeneration associated with Parkinson´s disease Maniscalchi A1, Funk M1,2, Benzi Juncos ON1,2, Alza NA1,3, Conde MA1,2,Uranga RM1,2, Salvador GA1,21Instituto de Investigaciones Bioquímicas de Bahía Blanca (INIBIBB), Universidad Nacional del Sur (UNS). 2Depto. de Biología, Bioquímica y Farmacia (DBByF-UNS), 3Depto. de Química (UNS). email: amaniscalchi@inibibb-conicet.gob.arFerroptosis 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 substancia nigra has been reported in PD. We have previously demonstrated that dopaminergic neurons exposed to α-synuclein overexpression and Fe overload display lipid dyshomeotasis that results in triacylglycerol (TAG) accumulation. Our goal in this work was to characterize 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 in several organ and tissues (brain, liver, kidney, and plasma) were evaluated.Motor skills were assessed by using open field and footprint tests. Mice exposed to Fe overload ( highest dose 1332 mg) showed a 60% diminution of total distance traveled, associated with a greater thigmotaxis (20%; p