LDL exposure disrupts mitochondrial function and dynamics in a hippocampal neuronal cell line

Abstract

Hypercholesterolemia has been associated with cognitive dysfunction and neurodegenerative disease. Moreover, this metabolic condition disrupts the blood-brain barrier, allowing Low-Density Lipoprotein (LDL) to enter the Central Nervous System. Thus, we investigated the effects of LDL exposure on mitochondrial function in a mouse hippocampal neuronal cell line (HT-22). HT-22 cells were exposed to human LDL (50 and 300 μg/mL) for 24 hours. After this, intracellular lipid droplet (LD) content, cell viability, cell death, and mitochondrial parameters were performed. We found that the higher LDL concentration LDL increases LD content compared to control. Both concentrations increased the number of Annexin V-positive cells, indicating apoptosis. Moreover, in mitochondrial parameters, the exposure of LDL on hippocampal neuronal cell line leads to a decrease in mitochondrial complexes I and II in both concentrations tested and a reduction in Mitotracker™ Red fluorescence and Mitotracker™ Red and Mitotracker™ Green ratio in the higher concentration, indicating dysfunction in the mitochondria. The LDL incubation induces mitochondrial superoxide production and a decrease in superoxide dismutase activity in the lower concentration in HT-22 cells. Finally, hippocampal neuronal cell line exposed to LDL exhibit an increase in the expression of genes associated with mitochondrial fusion (OPA1 and Mitofusin 2) in the lower concentration. In conclusion, our findings suggest that LDL exposure induces mitochondrial dysfunction and modulation in mitochondrial dynamics in the hippocampal neuronal cells.