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给4日龄大鼠幼崽注射乙醇后数小时内,小脑内特异于脑源性神经营养因子(BDNF)、p75神经营养因子受体(p75NTR)和酪氨酸激酶B受体(TrkB)亚型的信使核糖核酸(mRNA)会发生变化。

Alterations of cerebellar mRNA specific for BDNF, p75NTR, and TrkB receptor isoforms occur within hours of ethanol administration to 4-day-old rat pups.

作者信息

Ge Yun, Belcher Scott M, Light Kim E

机构信息

Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.

出版信息

Brain Res Dev Brain Res. 2004 Jul 19;151(1-2):99-109. doi: 10.1016/j.devbrainres.2004.04.002.

Abstract

Developing cerebellar Purkinje cells of the rat are extremely sensitive to ethanol during postnatal days (PN) 4-6, but not at later times during development. Ethanol exposure during this vulnerable window induces rapid apoptotic Purkinje cell death that is hypothesized to result from ethanol inhibition in brain-derived nerve growth factor (BDNF)-TrkB neurotrophic signaling that results in loss of apoptotic suppression. In this study, the effect that different concentrations of ethanol (1.5, 3.0, 4.5 and 6.0 g/kg) have on steady-state mRNA expression of BDNF and different TrkB receptor isoforms in the cerebellum on PN4 was determined at 1, 4, 6, and 8 h after treatment. Significant decreases in mRNA specific for BDNF and TrkB isoforms were detected within 1 h after ethanol administration. No significant alterations in expression of mRNA specific to the low affinity p75(NTR) receptor were identified. These alterations are concurrent with the PN4 vulnerable period for Purkinje cells since equivalent treatment of PN9 rat pups does not produce significant alterations in mRNA specific to BDNF or TrkB at 4 h after exposure. These results support the hypothesis that ethanol induces a disruption of BDNF-TrkB signaling that results in loss of apoptotic suppression in vulnerable Purkinje cells by growth factor withdrawal.

摘要

大鼠发育中的小脑浦肯野细胞在出生后第4至6天(PN)对乙醇极为敏感,但在发育后期则不然。在此易损期暴露于乙醇会诱导浦肯野细胞迅速发生凋亡性死亡,据推测这是由于乙醇抑制了脑源性神经生长因子(BDNF)-TrkB神经营养信号传导,导致凋亡抑制作用丧失所致。在本研究中,测定了不同浓度乙醇(1.5、3.0、4.5和6.0 g/kg)在处理后1、4、6和8小时对PN4小脑BDNF和不同TrkB受体亚型稳态mRNA表达的影响。乙醇给药后1小时内,检测到BDNF和TrkB亚型特异性mRNA显著下降。未发现低亲和力p75(NTR)受体特异性mRNA表达有明显改变。这些改变与PN4浦肯野细胞的易损期同时出现,因为对PN9幼鼠进行同等处理在暴露后4小时不会导致BDNF或TrkB特异性mRNA出现明显改变。这些结果支持了以下假说:乙醇诱导BDNF-TrkB信号传导中断,导致生长因子缺失,从而使易损的浦肯野细胞凋亡抑制作用丧失。

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