Traumatic brain injury (TBI) is a considerable cause of mild cognitive impairment and dementia. Intranasal administration of nerve growth factor (NGF) has previously been found to improve cognitive function after TBI, but the mechanism remains unclear. This study aimed to investigate the effects of intranasal NGF on the tau hyperphosphorylation following TBI. A modified Feeney's weight-drop model was used to induce TBI. Rats were randomly divided into control group, TBI group, TBI+NGF group, TBI+PDTC group and TBI+IL-1ra group. Rats in TBI+NGF group were administered with NGF (5 μg/d) for 3d before surgery. Hyperphosphorylated tau protein was remarkable in the peri-contusional cortex area with TBI. Both western blotting and immunostaining results displayed intranasal pretreatment of NGF significantly reduced tau phosphorylation. To evaluate the underlying mechanism, the levels of glycogen synthase kinase 3β (GSK-3β), interleukin-1β (IL-1β), and the DNA binding activity of nuclear factor-κB (NF-κB) were assayed. NGF markedly inhibited GSK-3β. NGF also reduced TBI-induced elevation of IL-1β and NF-κB DNA binding activity. Furthermore, PDTC and IL-1ra were injected to prove a potential signaling pathway among NF-κB, IL-1β and GSK-3β. Taken together, these findings demonstrated that intranasal NGF could effectively attenuate the hyperphosphorylation of tau after TBI, which might involve an integrated signaling pathway related to NF-κB.
Keywords: GSK-3β; IL-1β; Intranasal; Nerve growth factor; Tau; Traumatic brain injury.
Copyright © 2014. Published by Elsevier B.V.