Abstract: Objective: To investigate the neuroprotective effects of transforming growth factor beta 1(TGF-β1) on the expression and secretion of cytokines induced by Aβ_1-42 in hippocampal neurons and microglial co-cultures. Methods: Hippocampal neurons and microglia obtained from SD rat were co-cultured. TGF-β1 was applied on day 5 after the neurons and microglia co-cultures were incubated at the concentrations of 5 or 20 ng/ml, Aβ_1-42 was added 1 h following TGF-β1 application at a concentration of 5 μmol/L. They were incubated for 72 h and then assessed for further studies. Western blot analyses were employed to examine the expression of inducible nitric oxide synthase (iNOS); Real-time PCR and ELISA were used to detect the mRNA expression and secretion of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and insulin-like growth factor-1 (IGF-1). Results: In the hippocampal neuron-microglia co-cultures, Aβ_1-42 induced upregulation of iNOS, TNF-α and IL-1β, downregulation of IGF-1. TGF-β1 pretreatment ameliorated the pro-inflammatory effects caused by Aβ_1-42. Conclusion: TGF-β1 significantly inhibits the increase in inflammatory cytokines and the decrease in neurotrophic factor which are caused by Aβ_1-42-induced microglia activation.

Key words: TGF-β1, Aβ_1-42, microglia, hippocampal neurons, cytokines