Abstract: Previous studies have shown that fibroblast growth factor 13 is downregulated in the brain of both Alzheimer’s disease mouse models and patients, and that it plays a vital role in the learning and memory. However, the underlying mechanisms of fibroblast growth factor 13 in Alzheimer’s disease remain unclear. In this study, we established rat models of Alzheimer’s disease by stereotaxic injection of amyloid-β (Aβ1–42)-induced into bilateral hippocampus. We also injected lentivirus containing fibroblast growth factor 13 into bilateral hippocampus to overexpress fibroblast growth factor 13. The expression of fibroblast growth factor 13 was downregulated in the brain of the Alzheimer’s disease model rats. After overexpression of fibroblast growth factor 13, learning and memory abilities of the Alzheimer’s disease model rats were remarkably improved. Fibroblast growth factor 13 overexpression increased brain expression levels of oxidative stress-related markers glutathione, superoxide dismutase, phosphatidylinositol-3-kinase, AKT and glycogen synthase kinase 3β, and anti-apoptotic factor BCL. Furthermore, fibroblast growth factor 13 overexpression decreased the number of apoptotic cells, expression of pro-apoptotic factor BAX, cleaved-caspase 3 and amyloid-β expression, and levels of tau phosphorylation, malondialdehyde, reactive oxygen species and acetylcholinesterase in the brain of Alzheimer’s disease model rats. The changes were reversed by the phosphatidylinositol-3-kinase inhibitor LY294002. These findings suggest that overexpression of fibroblast growth factor 13 improved neuronal damage in a rat model of Alzheimer’s disease through activation of the phosphatidylinositol-3-kinase/AKT/glycogen synthase kinase 3β signaling pathway.

Key words: AKT, Alzheimer’s disease, amyloid-β, apoptosis, cognitive dysfunction, fibroblast growth factor 13, glycogen synthase kinase 3β, neuronal damage, oxidative stress, phosphatidylinositol-3-kinase