Ischemic conditions affect neutral lipid reshaping in Blood Brain Barrier cells.

Ischemic/reperfusion (I/R) injury contribution in Alzheimer’s Disease (AD) onset has definitely been endorsed in the last decades. Oxygen and nutrient deprivation occurring during I/R induced a signaling pathways remodeling with alteration in oxidative stress, inflammatory response initiation, protein and lipid homeostasis that can lead to blood brain barrier (BBB) break-down. Moreover starvation occurring during I/R is a condition leading to autophagy activation. Autophagy allows proteins and lipids degradation for abnormal material clearance or for amino acids and fatty acids recycling in proteins and lipids essential for survival. In the present study we monitored the lipid reshaping and peroxidation as well signaling pathway linked to those occurring under oxygen and glucose deprivation (OGD, an experimental condition mimicking cerebral ischemia), focusing on the autophagy involvement, in order to evaluate their contribute in BBB alteration/adaptation to the starvation. Rat brain endothelial (RBE4) were subjected to OGD treatment for 3 hours. After restoration of standard conditions for one or twenty-four hours (R1h and R24h respectively), lipids and proteins analyses were performed. Data obtained demonstrated that I/R injury induced a reshaping in triglycerides and in CE, along to lipid droplets (LD) biogenesis leading to an excessive lipid storage. In parallel, the increase of LC3-II/LC3-I ratio and LC3 co-localization with LD suggest that a specific autophagy, lipophagy, is activated to counteract the cell engulfment. Moreover, LD seemed to move towards plasma membrane following exocytosis pathways related or not to exophagy, a secretory path activated to eliminate misfolded proteins in neurons subjected to OGD [Lonati et al., J. Mol. Cell. 2018]. Nevertheless, unconventional spreading of abnormal material, activated against I/R harmful effects, might leads to neurodegeneration