Intranasal erythropoietin ameliorates neurological function impairments and neural pathology in mice with chronic alcoholism by regulating autophagy-related Nrf2 degradation

Nie Xuedan; Wang Wenbo; Wang QinZhu DanSong Hongshan

首页> 外文期刊>Molecular medicine reports >Intranasal erythropoietin ameliorates neurological function impairments and neural pathology in mice with chronic alcoholism by regulating autophagy-related Nrf2 degradation

【24h】

Intranasal erythropoietin ameliorates neurological function impairments and neural pathology in mice with chronic alcoholism by regulating autophagy-related Nrf2 degradation

机译：Intranasal erythropoietin ameliorates neurological function impairments and neural pathology in mice with chronic alcoholism by regulating autophagy-related Nrf2 degradation

获取原文

获取原文并翻译 | 示例

掌桥外文数据库（机构版） >>

开具论文收录证明 >>

文献代查 >>

页面导航

摘要
著录项
相关主题

摘要

The neurological disorders and neural pathology brought about by chronic alcoholism are difficult to be reversed. Increasing evidence highlights the protective roles of erythropoietin (EPO) in neurodegenerative diseases and injuries of the central nervous system. In the present study, we investigated the therapeutic effects of EPO on the neurological function deficits and neural pathology caused by chronic alcoholism and the regulatory mechanisms. Using the canonical mouse model of chronic alcohol exposure designed to mimic the repeated cycles of heavy abuse typical of chronic alcoholism, it was found that EPO delivered via intranasal route effectively restored the alcohol-impaired motor cooperation in rotarod and beam walk tests, reversed alcoholic cognitive and emotional alterations in the novel location recognition task and open-filed test, and rescued alcohol-disrupted nervous conduction in the somatosensory-evoked potential (SSEP) test. Consistently, the intranasally administered EPO promoted the remyelination and synapse formation in chronic alcohol-affected neocortex and hippocampus as evidenced by immunofluorescence staining and transmission electron microscopy. Additionally, we discovered that the exogenous rhEPO, which entered the cerebrum through intranasal route, activated the erythropoietin receptor (EPOR) and the downstream ERKs and PI3K/AKT signaling, and suppressed autophagy-related degradation of nuclear factor, erythroid 2-like 2 (Nrf2). Furthermore, the intranasal EPO-exerted neuroprotection was almost abolished when the specific Nrf2 antagonist ATRA was administered intraperitoneally prior to intranasal EPO treatment. Collectively, our data demonstrated the repairing potential of EPO for the neurological disorders and neural pathology caused by chronic alcoholism, and identified the Nrf2 activity as the key mechanism mediating the protective effects of EPO.

著录项

来源
《Molecular medicine reports》 |2019年第2期|1139-1149|共11页
作者
Nie Xuedan; Wang Wenbo; Wang QinZhu DanSong Hongshan;
展开▼
作者单位

Harbin Med Univ, Affiliated Hosp 2, Dept Neurol, Harbin 150001, Heilongjiang, Peoples R China;

Qiqihar Med Univ, Daqing Longnan Hosp, Affiliated Hosp 5, Intens Care Unit, Daqing 163453;

Harbin Med Univ, Affiliated Hosp 2, Dept Nephrol, Harbin 150001, Heilongjiang, Peoples R ChinaQiqihar Med Univ, Daqing Longnan Hosp, Affiliated Hosp 5, Dept Neurol, 35 Aiguo Rd, Daqing 163453;

展开▼
收录信息
原文格式 PDF
正文语种英语
中图分类基础医学;
关键词
erythropoietin; chronic alcoholism; neurological function deficits; Nrf2; autophagy;

Intranasal erythropoietin ameliorates neurological function impairments and neural pathology in mice with chronic alcoholism by regulating autophagy-related Nrf2 degradation

摘要

著录项

相关主题

期刊订阅