title: Intranasal nerve growth factor attenuates tau phosphorylation in brain after traumatic brain injury in rats.
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 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.
authors.affiliation: Department of Neurology, Jinling Hospital, Nanjing University School of Medicine, Jiangsu Province 210002, China.
authors.forename: Qiushi
authors.initials: Q
authors.lastname: Lv
authors.affiliation: Department of Neurology, Jinling Hospital, Nanjing University School of Medicine, Jiangsu Province 210002, China.
authors.forename: Wenya
authors.initials: W
authors.lastname: Lan
authors.affiliation: Department of Neurology, Jinling Hospital, Nanjing University School of Medicine, Jiangsu Province 210002, China.
authors.forename: Wenshan
authors.initials: W
authors.lastname: Sun
authors.affiliation: Department of Neurology, Jinling Hospital, Nanjing University School of Medicine, Jiangsu Province 210002, China.
authors.forename: Ruidong
authors.initials: R
authors.lastname: Ye
authors.affiliation: Department of Neurology, Jinling Hospital, Nanjing University School of Medicine, Jiangsu Province 210002, China.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Fan
authors.affiliation: Department of Neurology, Jinling Hospital, Nanjing University School of Medicine, Jiangsu Province 210002, China.
authors.forename: Minmin
authors.initials: M
authors.lastname: Ma
authors.affiliation: Department of Neurology, Jinling Hospital, Nanjing University School of Medicine, Jiangsu Province 210002, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Yin
authors.affiliation: Department of Neurology, Jinling Hospital, Nanjing University School of Medicine, Jiangsu Province 210002, China.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Neurology, Jinling Hospital, Nanjing University School of Medicine, Jiangsu Province 210002, China.
authors.forename: Gelin
authors.initials: G
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Jianwu
authors.initials: J
authors.lastname: Dai
authors.affiliation: Department of Neurology, Jinling Hospital, Nanjing University School of Medicine, Jiangsu Province 210002, China. Electronic address: grb1995@163.com.
authors.forename: Ruibing
authors.initials: R
authors.lastname: Guo
authors.affiliation: Department of Neurology, Jinling Hospital, Nanjing University School of Medicine, Jiangsu Province 210002, China. Electronic address: xfliu2@viop.163.com.
authors.forename: Xinfeng
authors.initials: X
authors.lastname: Liu
mesh_terms: D000281:Administration, Intranasal; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000187:drug effects*; D001930:Brain Injuries / Q000188:drug therapy* / Q000473:pathology*; D004195:Disease Models, Animal; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation / Q000187:drug effects; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D008297:Male; D020932:Nerve Growth Factor / Q000008:administration & dosage*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D053583:Interleukin-1beta; D009687:Nuclear Proteins; D012333:RNA, Messenger; D016875:tau Proteins; D020932:Nerve Growth Factor; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D038362:Glycogen Synthase Kinase 3
keywords: GSK-3β; IL-1β; Intranasal; Nerve growth factor; Tau; Traumatic brain injury