Chronic Neuroinflammation Induced by Lipopolysaccharide Injection into the Third Ventricle Induces Behavioral Changes.
J Mol Neurosci
; 71(6): 1306-1319, 2021 Jun.
Article
in En
| MEDLINE
| ID: mdl-33405196
ABSTRACT
The 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 Aß1-40/42 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 throughout 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 acceleration 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-1ß, 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 depressive-like symptoms and that the loss of cholesterol might be a biomarker of chronic neuroinflammation. The lack of pathological hallmarks of AD in our model indicates that Gram-negative bacteria infection might not be a single cause of AD.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Maze Learning
/
Encephalitis
Type of study:
Etiology_studies
/
Prognostic_studies
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
J Mol Neurosci
Journal subject:
BIOLOGIA MOLECULAR
/
NEUROLOGIA
Year:
2021
Document type:
Article
Affiliation country: