p75NTR Promotes Astrocyte Proliferation in Response to Cortical Stab Wound
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ORIGINAL RESEARCH
p75NTR Promotes Astrocyte Proliferation in Response to Cortical Stab Wound Mingming Chen1 · Linlu Guo1 · Jie Hao1 · Jie Ni1 · Qunyu Lv1 · Xiaoyan Xin2 · Hong Liao1 Received: 15 July 2020 / Accepted: 11 November 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Astrogliosis after brain trauma can have a significant impact on functional recovery. However, little is known about the mechanisms underlying astrocyte proliferation and subsequent astrogliosis. In this study, we established a cortical stab wound injury mouse model and observed dramatic astrocyte activation and nerve growth factor receptor (p75NTR) upregulation near the lesion. We also found profound alterations in the cell cycle of astrocytes near the lesion, with a switch from a mitotically quiescent (G0) phase to the G2/M and S phases. However, no changes in the level of astrocyte apoptosis were observed. Cell cycle progression to the G2/M and S phases and CDK2 protein levels in response to cortical stab wound was inhibited after p75NTR knockdown in mouse astrocytes. Conversely, p75NTR overexpression in mouse astrocytes was sufficient in promoting cell cycle progression. In conclusion, our results suggested that p75NTR upregulation in astrocytes after brain injury induces cell cycle entry by promoting CDK2 expression and promoting astrocyte proliferation. Our findings provided a better understanding of astrocytic responses after cortical stab wound injury in mice. Keywords p75NTR · Traumatic brain injury · Astrocyte · Proliferation · Cell cycle · CDK2
Introduction Traumatic brain injury (TBI) is a leading cause of disability and death in civilian and military populations around the world according to the World Health Organization (WHO) estimate, but there are no better therapeutic strategies in response to TBI, especially stab wound injury (Carroll et al. 2004; Smith et al. 2019). Astrogliosis occurs quickly Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10571-020-01006-x) contains supplementary material, which is available to authorized users.
after primary injury and is considered as one of obvious pathological hallmarks after stab wound injury, which is a process of astrocytes undergoing a series of morphological and functional alteration, and influences neuronal functions and behaviors (Burda et al. 2016; Zhou et al. 2020). Astrogliosis has been regarded to be predominantly harmful by triggering contact- and diffusion-mediated molecules to help the entry of inflammatory cells, recruitment of leukocytes into central nervous system (CNS) and disruption in blood–brain barrier (BBB, Chodobski et al. 2011; Zamanian et al. 2012; Hamby et al. 2012), while some evidence also
* Hong Liao [email protected]
Xiaoyan Xin [email protected]
Mingming Chen [email protected]
1
New Drug Screening Center, Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, No. 24 Tongjiaxiang Street, Nanjing 2
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