Chronic Neuroinflammation Induced by Lipopolysaccharide Injection into the Third Ventricle Induces Behavioral Changes

AbstractThe existence of Gram-negative bacteria in the brain, regardless of underlying immune status has been demonstrated by recent studies. The colocalization of lipopolysaccharide (LPS) with A β1-40/42 in amyloid plaques supports the hypothesis that brain microbes may be the cause, triggering chronic neuroinflammation, leading to Alzheimer ’s disease (AD). To investigate the behavioral changes induced by infectious neuroinflammation, we chose the third ventricle as the site of a single LPS injection (20 μg or 80 μg) in male Wistar rats to avoid mechanical injury to forebrain structures while inducing widespread inflammation thro ughout the brain. Chronic neuroinflammation induced by LPS resulted in depressive-like behaviors and the impairment of spatial learning; however, there was no evidence of the development of pathological hallmarks (e.g., the phosphorylation of tau) for 10 months following LPS injection. The accelera tion of cholesterol metabolism via CYP46A1 and the retardation of cholesterol synthesis via HMGCR were observed in the hippocampus of rats treated with either low-dose or high-dose LPS. The rate-limiting enzymes of cholesterol metabolism (CYP46A1) in SH-SY5Y cells and synthesis (HMGCR) in U251 cells were altered by inflammation stimulators, including LPS, IL-1β, and TNF-α, through the TLR4/MyD88/NF-κB signaling pathway. The data suggest that chronic neuroinflammation provoked by the administration of LPS into the third ventricle may induce dep...
Source: Journal of Molecular Neuroscience - Category: Neuroscience Source Type: research