Nanotechnology as a therapeutic strategy to prevent neuropsychomotor alterations associated with hypercholesterolemia

Hypercholesterolemia has been linked to neurodegenerative disease development. Previously others and we demonstrated that high levels of plasma cholesterol-induced memory impairments and depressive-like behavior in mice. More recently, some evidence reported that a hypercholesterolemic diet led to motor alterations in rodents. Peripheral inflammation, blood-brain barrier (BBB) dysfunction, and neuroinflammation seem to be the connective factors between hypercholesterolemia and brain disorders. Herein, we aimed to investigate whether treatment with gold nanoparticles (GNPs) can prevent the inflammation, BBB disruption, and behavioral changes related to neurodegenerative diseases and depression, induced by hypercholesterolemic diet intake in mice. Adult Swiss mice were fed a standard or a high cholesterol diet for eight weeks and concomitantly treated with either vehicle or GNPs by the oral route. At the end of treatments, mice were subjected to behavioral tests. After that, the blood, liver, and brain structures were collected for biochemical analysis. The high cholesterol diet-induced an increase in the plasma cholesterol levels and body weight of mice, which were not modified by GNPs treatment. Hypercholesterolemia was associated with enhanced liver tumor necrosis factor- α (TNF-α), BBB dysfunction in the hippocampus and olfactory bulb, memory impairment, cataleptic posture, and depressive-like behavior. Notably, GNPs administration attenuated liver inflammation, BBB dysfunction, and improved behavioral and memory deficits in hypercholesterolemic mice. Also, GNPs increased mitochondrial complex I activity in the prefrontal cortex of mice. It is worth highlight that GNPs' administration did not cause toxic effects in the liver and kidney of mice. Overall, our results indicated that GNPs treatment potentially mitigated peripheral, brain, and memory impairments related to hypercholesterolemia.