p75NTR在颅脑放疗后海马神经发生损伤中的作用

doi:10.3760/cma.j.issn.1004-4221.2018.08.010

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Abstract

Objective To investigate the role of p75 neurotrophin receptor (p75NTR) in the irradiation-induced hippocampal neurogenesis impairment. Methods Thirty Sprague-Dawley rats were subject to whole brain irradiation with a single dose of 10 Gy 4 MeV electron beam. At 1 month after irradiation,the hippocampal tissues of the rats were collected. Western blot was used to detect the changes in the expression level of p75NTR protein. Immunofluorescence confocal laser microscopy was performed to observe the variations in the hippocampal neurogenesis. The stereotatic method was adopted for intra-hippocampal injection of AAV-shp75NTR to specifically knock out p75NTR.The relationship between p75NTR and hippocampal neurogenesis was analyzed. Results Western blot demonstrated that the expression of p75NTR protein was significantly up-regulated by 43.8% after irradiation (P<0.05).Immunofluorescent staining showed that the quantity of BrdU⁺NeuN⁺ cells in rats was significantly decreased by 81.5% at 1 month after irradiation compared with that in the control group (P<0.01).After the specific knockout of p75NTR,hippocampal neurogenesis was obviously protected. Conclusions p75NTR plays a pivotal role in the irradiation-induced hippocampal neurogenesis impairment.

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	Articles by authors
	Ji Shengjun
	Ding Xin
	Wu Haohao
	Zhang Qixian
	Chen Qingqing
	Zhang Junjun
	Cai Shang
	Tian Ye

Key words： Neurotrophin receptor Neurogenesis Hippocampus Irradiation Rat

Received: 18 December 2017

Corresponding Authors: Tian Ye,Email:dryetian@126.com

Cite this article:

Ji Shengjun,Ding Xin,Wu Haohao et al. The role of p75 neurotrophin receptor in hippocampal neurogenesis impairment after cranial irradiation[J]. Chinese Journal of Radiation Oncology, 2018, 27(8): 759-762.

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http://journal12.magtechjournal.com/Jweb_fszlx/EN/10.3760/cma.j.issn.1004-4221.2018.08.010 OR http://journal12.magtechjournal.com/Jweb_fszlx/EN/Y2018/V27/I8/759

[1] Gon alves JT,Schafer ST,Gage FH.Adult Neurogenesis in the Hippocampus:from stem cells to behavior[J].Cell,2016,167(4):897-914.DOI:10.1016/j.cell.2016.10.021.
[2] Cameron HA,Glover LR.Adult neurogenesis:beyond learning and memory[J].Annu Rev Psychol,2015,66:53-81.DOI:10.1146/annurev-psych-010814-015006.
[3] Ji S,Tian Y,Lu Y,et al. Irradiation-induced hippocampal neurogenesis impairment is associated with epigenetic regulation of bdnf gene transcription[J].Brain Res,2014,1577:77-88.DOI:10.1016/j.brainres.2014.06.035.
[4] Monje M,Dietrich J.Cognitive side effects of cancer therapy demonstrate a functional role for adult neurogenesis[J].Behav Brain Res,2012,227(2):376-379.DOI:10.1016/j.bbr.2011.05.012.
[5] Makale MT,McDonald CR,Hattangadi-Gluth JA,et al. Mechanisms of radiotherapy-associated cognitive disability in patients with brain tumours[J].Nat Rev Neurol,2017,13(1):52-64.DOI:10.1038/nrneurol.2016.185.
[6] 黄国栋,罗鸣,屈晓飞,等.电离辐射抑制海马区神经发生与放射性脑损伤认知损害的关系[J].中华放射医学与防护杂志,2013,33(2):113-118.DOI:10.3760/cma.j.issn.0254-5098.2013.02.001.
[7] Shi J,Longo FM,Massa SM.A small molecule p75(NTR) ligand protects neurogenesis after traumatic brain injury[J].Stem Cells,2013,31(11):2561-2574.DOI:10.1002/stem.1516.
[8] Sabry MA,Fares M,Folkesson R,et al. Commentary:Impact of a deletion of the full-length and short isoform of p75NTR on cholinergic innervation and the population of postmitotic doublecortin positive cells in the dentate gyrus[J].Front Neuroanat,2016,10:14.DOI:10.3389/fnana.2016.00014.
[9] Greene-Schloesser D,Robbins ME,Peiffer AM,et al. Radiation-induced brain injury:a review[J].Front Oncol,2012,2:73.DOI:10.3389/fonc.2012.00073.
[10] Wu PH,Coultrap S,Pinnix C,et al. Radiation induces acute alterations in neuronal function[J/OL].PLoS One,2012,7(5):e37677.DOI:10.1371/journal.pone.0037677.
[11] 孙锐,张力元,冀胜军,等.10 cGy单次全脑照射引起大鼠认知功能损害的初步实验研究[J].中华放射肿瘤学杂志,2012,21(5):474-476.DOI:10.3760/cma.j.issn.1004-4221.2012.05.023.
[12] Rostami E,Krueger F,Plantman S,et al. Alteration in BDNF and its receptors,full-length and truncated TrkB and p75(NTR) following penetrating traumatic brain injury[J].Brain Res,2014,1542:195-205.DOI:10.1016/j.brainres.2013.10.047.
[13] Shulga A,Magalh es AC,Autio H,et al. The loop diuretic bumetanide blocks posttraumatic p75NTR upregulation and rescues injured neurons[J].J Neurosci,2012,32(5):1757-1770.DOI:10.1523/JNEUROSCI.3282-11.2012.
[14] Naumann T,Casademunt E,Hollerbach E,et al. Complete deletion of the neurotrophin receptor p75NTR leads to long-lasting increases in the number of basal forebrain cholinergic neurons[J].J Neurosci,2002,22(7):2409-2418.DOI:20026171.
[15] Brito V,Giralt A,Enriquez-Barreto L,et al. Neurotrophin receptor p75(NTR) mediates Huntington′s disease-associated synaptic and memory dysfunction[J].J Clin Invest,2014,124(10):4411-4428.DOI:10.1172/JCI74809.