Rapamycin inhibits lipopolysaccharide-induced neuroinflammation in vitro and in vivo

Alzheimer's disease (AD) is the most common type of progressive neurodegenerative disorder, and is responsible for the most common form of dementia in the elderly. Inflammation occurs in the brains of patients with AD, and is critical for disease progression. In the present study, the effects of rapamycin (RAPA) on neuroinflammation lipopolysaccharide (LPS)-induced were investigated. SH-SY5Y human neuroblastoma cells were treated with 20 mu g/ml LPS and 0.1, 1 or 10 nmol/l RAPA, and were analyzed at various time points (6, 12 and 24 h). The mRNA expression levels of interleukin (IL) 1 beta, IL6 and hypoxia-inducible factor l alpha (HIF1 alpha) were determined using reverse transcription-quantitative polymerase chain reaction. The protein expression levels of phosphorylated (p-)S6, p-nuclear factor kappa B (NF kappa B), p-inhibitor of NF kappa B kinase subunit beta (IKK beta) and p-tau protein were measured by western blot analysis. p-IKK beta, p-NF kappa B, p-S6 and p-tau were significantly decreased at 6, 12 and 24 h when cells were treated with >= 0.1 nmol/ml RAPA. In addition, female Sprague Dawley rats were intracranially injected with a single dose of 100 mu g/kg LPS in the absence or presence of 1 mg/kg RAPA pretreatment. Brain tissues were subjected to immunohistochemical analysis 6-24 h later, which revealed that the expression levels of HIF1 alpha and p-S6 in rat cerebral cortex were increased following LPS injection; however, this increase was abrogated by RAPA treatment. RAPA may therefore be considered a potential therapeutic agent for the early or emergency treatment of neuroinflammation.