Highlights
- •Nerve growth factor reduces tau hyperphosphorylation after traumatic brain injury.
- •Nerve growth factor decreases the GSK-3β activation in traumatic brain injury rats.
- •Nerve growth factor lowers the IL-1β and NF-κB in traumatic brain injury rats.
- •The inhibition of NF-κB/IL-1β/GSK-3β affects the reduction of phosphorylation tau.
- •Our observation provides a novel insight on the effect of NGF in TBI.
Abstract
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 3 d 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
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Article info
Publication history
Published online: June 24, 2014
Accepted:
June 13,
2014
Received in revised form:
May 15,
2014
Received:
October 31,
2013
Identification
Copyright
© 2014 Published by Elsevier Inc.
