Chronic Neuroinflammation Induced by Lipopolysaccharide Injection into the Third Ventricle Induces Behavioral Changes
| Autor: | Xuejiao Duan, Zheqiong Yang, Ke Xue, Ke Li, Shufang Na, Shuwei Tian, Rongyan Wang, Yanjie Fan, Jiang Yue |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Lipopolysaccharides
Male 0301 basic medicine medicine.medical_specialty Lipopolysaccharide Interleukin-1beta Hippocampus tau Proteins Inflammation 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound 0302 clinical medicine Cell Line Tumor Internal medicine Cholesterol 24-Hydroxylase Animals Humans Medicine Rats Wistar Maze Learning Neuroinflammation Injections Intraventricular Tumor Necrosis Factor-alpha business.industry Colocalization General Medicine Rats Toll-Like Receptor 4 Cholesterol 030104 developmental biology Endocrinology chemistry Forebrain TLR4 Encephalitis Hydroxymethylglutaryl CoA Reductases lipids (amino acids peptides and proteins) Signal transduction medicine.symptom business 030217 neurology & neurosurgery |
| Zdroj: | Journal of Molecular Neuroscience. 71:1306-1319 |
| ISSN: | 1559-1166 0895-8696 |
| Popis: | 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 Aβ1-40/42 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-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 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. |
| Databáze: | OpenAIRE |
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