Widespread hyperphosphorylated tau in the working memory circuit early after cortical impact injury of brain (Original study).
A series of neurological and psychiatric symptoms occur after traumatic brain injury (TBI), with cognitive dysfunction being one of the most prominent sequela. Given that tau hyperphosphorylation is an important cause of cognitive impairment in patients of Alzheimer's disease, our present study detected the presence of hyperphosphorylated tau (p-tau), mainly at Ser404, in multiple brain regions, including the ipsilateral parietal cortex, contralateral hippocampus and prefrontal cortex, immediately after the injury in a mouse TBI model; these changes lasted for at least 4w. All of these brain regions play important roles in working memory. Hyperphosphorylated tau protein was primarily located in neurons and was accompanied by axonal injury and dendritic spine degeneration. Our study demonstrated that p-tau spreads gradually and selectively from the injured cortex to other brain regions after TBI and that all of the affected regions are part of the working memory circuit. These findings provide experimental support for the role of p-tau in cognitive impairment in the early phase after TBI.
Molecular Biology Center, State Key Laboratory of Trauma, Burn, and Combined Injury, Research Institute of Surgery and Daping Hospital, Third Military Medical University, Chongqing 400042, China. Electronic address: zhaoziai@hotmail.com.
Zi-Ai
ZA
Zhao
Molecular Biology Center, State Key Laboratory of Trauma, Burn, and Combined Injury, Research Institute of Surgery and Daping Hospital, Third Military Medical University, Chongqing 400042, China. Electronic address: leona.ning@gmail.com.
Ya-Lei
YL
Ning
Molecular Biology Center, State Key Laboratory of Trauma, Burn, and Combined Injury, Research Institute of Surgery and Daping Hospital, Third Military Medical University, Chongqing 400042, China. Electronic address: Ping__ping0074@sina.com.
Ping
P
Li
Molecular Biology Center, State Key Laboratory of Trauma, Burn, and Combined Injury, Research Institute of Surgery and Daping Hospital, Third Military Medical University, Chongqing 400042, China. Electronic address: yangnan831113@163.com.
Nan
N
Yang
Molecular Biology Center, State Key Laboratory of Trauma, Burn, and Combined Injury, Research Institute of Surgery and Daping Hospital, Third Military Medical University, Chongqing 400042, China. Electronic address: pengyan1006@126.com.
Yan
Y
Peng
Molecular Biology Center, State Key Laboratory of Trauma, Burn, and Combined Injury, Research Institute of Surgery and Daping Hospital, Third Military Medical University, Chongqing 400042, China. Electronic address: xiong_ren_ping@163.com.
Ren-Ping
RP
Xiong
Molecular Biology Center, State Key Laboratory of Trauma, Burn, and Combined Injury, Research Institute of Surgery and Daping Hospital, Third Military Medical University, Chongqing 400042, China. Electronic address: zhaoyanname@hotmail.com.
Yan
Y
Zhao
Trauma Center, State Key Laboratory of Trauma, Burn, and Combined Injury, Research Institute of Surgery and Daping Hospital, Third Military Medical University, Chongqing 400042, China. Electronic address: liudong1107@live.cn.
Dong
D
Liu
Molecular Biology Center, State Key Laboratory of Trauma, Burn, and Combined Injury, Research Institute of Surgery and Daping Hospital, Third Military Medical University, Chongqing 400042, China. Electronic address: zengxujia1@yeah.net.
Xu-Jia
XJ
Zeng
Department of Neurology and Pharmacology, Boston University School of Medicine, Boston, MA, 02118, USA. Electronic address: chenjf@bu.edu.
Jiang-Fan
JF
Chen
Molecular Biology Center, State Key Laboratory of Trauma, Burn, and Combined Injury, Research Institute of Surgery and Daping Hospital, Third Military Medical University, Chongqing 400042, China. Electronic address: yuanguo.zhou@gmail.com.
Yuan-Guo
YG
Zhou
D000818:Animals; D001369:Axons / Q000473:pathology; D000070642:Brain Injuries, Traumatic / Q000378:metabolism* / Q000473:pathology; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology; D003712:Dendrites / Q000473:pathology; D008297:Male; D008570:Memory, Short-Term / Q000502:physiology*; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D016875:tau Proteins / Q000378:metabolism*
C558298:Mapt protein, mouse; D016875:tau Proteins
Controlled cortical impact; Tau protein; Traumatic brain injury