Traumatic brain injury stimulates neural stem cell proliferation via mammalian target of rapamycin signaling pathway activation

Xiaoting Wang, Pich Seekaew, Xiang Gao, Jinhui Chen

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Neural stem cells in the adult brain possess the ability to remain quiescent until needed in tissue homeostasis or repair. It was previously shown that traumatic brain injury (TBI) stimulated neural stem cell (NSC) proliferation in the adult hippocampus, indicating an innate repair mechanism, but it is unknown how TBI promotes NSC proliferation. In the present study, we observed dramatic activation of mammalian target of rapamycin complex 1 (mTORC1) in the hippocampus of mice with TBI from controlled cortical impact (CCI). The peak of mTORC1 activation in the hippocampal subgranular zone, where NSCs reside, is 24-48 h after trauma, correlating with the peak of TBI-enhanced NSC proliferation. By use of a Nestin-GFP transgenic mouse, in which GFP is ectopically expressed in the NSCs, we found that TBI activated mTORC1 in NSCs. With 5-bromo-2′-deoxyuridine labeling, we observed that TBI increased mTORC1 activation in proliferating NSCs. Furthermore, administration of rapamycin abolished TBI-promoted NSC proliferation. Taken together, these data indicate that mTORC1 activation is required for NSC proliferation postinjury, and thus might serve as a therapeutic target for interventions to augment neurogenesis for brain repair after TBI.

Original languageEnglish (US)
Article numbere0162-16.2016
JournaleNeuro
Volume3
Issue number5
DOIs
StatePublished - Sep 1 2016

Fingerprint

Neural Stem Cells
Sirolimus
Cell Proliferation
Hippocampus
Nestin
Traumatic Brain Injury
Neurogenesis
Brain
Bromodeoxyuridine
Transgenic Mice
Homeostasis
mechanistic target of rapamycin complex 1
Wounds and Injuries

Keywords

  • Mammalian target of rapamycin
  • Neural stem/progenitor cells
  • Proliferation
  • Quiescence
  • Traumatic brain injury

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Traumatic brain injury stimulates neural stem cell proliferation via mammalian target of rapamycin signaling pathway activation. / Wang, Xiaoting; Seekaew, Pich; Gao, Xiang; Chen, Jinhui.

In: eNeuro, Vol. 3, No. 5, e0162-16.2016, 01.09.2016.

Research output: Contribution to journalArticle

@article{9713ac0efb914784877eece2bca8c7fa,
title = "Traumatic brain injury stimulates neural stem cell proliferation via mammalian target of rapamycin signaling pathway activation",
abstract = "Neural stem cells in the adult brain possess the ability to remain quiescent until needed in tissue homeostasis or repair. It was previously shown that traumatic brain injury (TBI) stimulated neural stem cell (NSC) proliferation in the adult hippocampus, indicating an innate repair mechanism, but it is unknown how TBI promotes NSC proliferation. In the present study, we observed dramatic activation of mammalian target of rapamycin complex 1 (mTORC1) in the hippocampus of mice with TBI from controlled cortical impact (CCI). The peak of mTORC1 activation in the hippocampal subgranular zone, where NSCs reside, is 24-48 h after trauma, correlating with the peak of TBI-enhanced NSC proliferation. By use of a Nestin-GFP transgenic mouse, in which GFP is ectopically expressed in the NSCs, we found that TBI activated mTORC1 in NSCs. With 5-bromo-2′-deoxyuridine labeling, we observed that TBI increased mTORC1 activation in proliferating NSCs. Furthermore, administration of rapamycin abolished TBI-promoted NSC proliferation. Taken together, these data indicate that mTORC1 activation is required for NSC proliferation postinjury, and thus might serve as a therapeutic target for interventions to augment neurogenesis for brain repair after TBI.",
keywords = "Mammalian target of rapamycin, Neural stem/progenitor cells, Proliferation, Quiescence, Traumatic brain injury",
author = "Xiaoting Wang and Pich Seekaew and Xiang Gao and Jinhui Chen",
year = "2016",
month = "9",
day = "1",
doi = "10.1523/ENEURO.0162-16.2016",
language = "English (US)",
volume = "3",
journal = "eNeuro",
issn = "2373-2822",
publisher = "Society for Neuroscience",
number = "5",

}

TY - JOUR

T1 - Traumatic brain injury stimulates neural stem cell proliferation via mammalian target of rapamycin signaling pathway activation

AU - Wang, Xiaoting

AU - Seekaew, Pich

AU - Gao, Xiang

AU - Chen, Jinhui

PY - 2016/9/1

Y1 - 2016/9/1

N2 - Neural stem cells in the adult brain possess the ability to remain quiescent until needed in tissue homeostasis or repair. It was previously shown that traumatic brain injury (TBI) stimulated neural stem cell (NSC) proliferation in the adult hippocampus, indicating an innate repair mechanism, but it is unknown how TBI promotes NSC proliferation. In the present study, we observed dramatic activation of mammalian target of rapamycin complex 1 (mTORC1) in the hippocampus of mice with TBI from controlled cortical impact (CCI). The peak of mTORC1 activation in the hippocampal subgranular zone, where NSCs reside, is 24-48 h after trauma, correlating with the peak of TBI-enhanced NSC proliferation. By use of a Nestin-GFP transgenic mouse, in which GFP is ectopically expressed in the NSCs, we found that TBI activated mTORC1 in NSCs. With 5-bromo-2′-deoxyuridine labeling, we observed that TBI increased mTORC1 activation in proliferating NSCs. Furthermore, administration of rapamycin abolished TBI-promoted NSC proliferation. Taken together, these data indicate that mTORC1 activation is required for NSC proliferation postinjury, and thus might serve as a therapeutic target for interventions to augment neurogenesis for brain repair after TBI.

AB - Neural stem cells in the adult brain possess the ability to remain quiescent until needed in tissue homeostasis or repair. It was previously shown that traumatic brain injury (TBI) stimulated neural stem cell (NSC) proliferation in the adult hippocampus, indicating an innate repair mechanism, but it is unknown how TBI promotes NSC proliferation. In the present study, we observed dramatic activation of mammalian target of rapamycin complex 1 (mTORC1) in the hippocampus of mice with TBI from controlled cortical impact (CCI). The peak of mTORC1 activation in the hippocampal subgranular zone, where NSCs reside, is 24-48 h after trauma, correlating with the peak of TBI-enhanced NSC proliferation. By use of a Nestin-GFP transgenic mouse, in which GFP is ectopically expressed in the NSCs, we found that TBI activated mTORC1 in NSCs. With 5-bromo-2′-deoxyuridine labeling, we observed that TBI increased mTORC1 activation in proliferating NSCs. Furthermore, administration of rapamycin abolished TBI-promoted NSC proliferation. Taken together, these data indicate that mTORC1 activation is required for NSC proliferation postinjury, and thus might serve as a therapeutic target for interventions to augment neurogenesis for brain repair after TBI.

KW - Mammalian target of rapamycin

KW - Neural stem/progenitor cells

KW - Proliferation

KW - Quiescence

KW - Traumatic brain injury

UR - http://www.scopus.com/inward/record.url?scp=85028922706&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85028922706&partnerID=8YFLogxK

U2 - 10.1523/ENEURO.0162-16.2016

DO - 10.1523/ENEURO.0162-16.2016

M3 - Article

C2 - 27822507

AN - SCOPUS:85028922706

VL - 3

JO - eNeuro

JF - eNeuro

SN - 2373-2822

IS - 5

M1 - e0162-16.2016

ER -