Molecular mechanism of tumour necrosis factor alpha regulates hypocretin (orexin) expression, sleep and behaviour
被引:18
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作者:
Zhan, Shuqin
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机构:
Capital Med Univ, Xuanwu Hosp, Dept Neurol, Beijing 100053, Peoples R China
Beijing Key Lab Neuromodulat, Beijing, Peoples R ChinaCapital Med Univ, Xuanwu Hosp, Dept Neurol, Beijing 100053, Peoples R China
Zhan, Shuqin
[1
,2
]
Che, Pulin
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机构:
Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA
Univ Alabama Birmingham, Neurol, Birmingham, AL USACapital Med Univ, Xuanwu Hosp, Dept Neurol, Beijing 100053, Peoples R China
Che, Pulin
[3
,4
]
Zhao, Xue-ke
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机构:
Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USACapital Med Univ, Xuanwu Hosp, Dept Neurol, Beijing 100053, Peoples R China
Zhao, Xue-ke
[3
]
Li, Ning
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机构:
Capital Med Univ, Xuanwu Hosp, Dept Neurol, Beijing 100053, Peoples R China
Beijing Key Lab Neuromodulat, Beijing, Peoples R ChinaCapital Med Univ, Xuanwu Hosp, Dept Neurol, Beijing 100053, Peoples R China
Li, Ning
[1
,2
]
Ding, Yan
论文数: 0引用数: 0
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机构:
Capital Med Univ, Xuanwu Hosp, Dept Neurol, Beijing 100053, Peoples R China
Beijing Key Lab Neuromodulat, Beijing, Peoples R ChinaCapital Med Univ, Xuanwu Hosp, Dept Neurol, Beijing 100053, Peoples R China
Ding, Yan
[1
,2
]
Liu, Jianghong
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机构:
Capital Med Univ, Xuanwu Hosp, Dept Neurol, Beijing 100053, Peoples R China
Beijing Key Lab Neuromodulat, Beijing, Peoples R ChinaCapital Med Univ, Xuanwu Hosp, Dept Neurol, Beijing 100053, Peoples R China
Liu, Jianghong
[1
,2
]
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机构:
Li, Spring
[3
]
Ding, Karyn
论文数: 0引用数: 0
h-index: 0
机构:
Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USACapital Med Univ, Xuanwu Hosp, Dept Neurol, Beijing 100053, Peoples R China
Ding, Karyn
[3
]
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机构:
Han, Lynn
[3
]
Huang, Zhaoyang
论文数: 0引用数: 0
h-index: 0
机构:
Capital Med Univ, Xuanwu Hosp, Dept Neurol, Beijing 100053, Peoples R China
Beijing Key Lab Neuromodulat, Beijing, Peoples R ChinaCapital Med Univ, Xuanwu Hosp, Dept Neurol, Beijing 100053, Peoples R China
Huang, Zhaoyang
[1
,2
]
Wu, Liyong
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机构:
Capital Med Univ, Xuanwu Hosp, Dept Neurol, Beijing 100053, Peoples R ChinaCapital Med Univ, Xuanwu Hosp, Dept Neurol, Beijing 100053, Peoples R China
Wu, Liyong
[1
]
Wang, Yuping
论文数: 0引用数: 0
h-index: 0
机构:
Capital Med Univ, Xuanwu Hosp, Dept Neurol, Beijing 100053, Peoples R China
Beijing Key Lab Neuromodulat, Beijing, Peoples R ChinaCapital Med Univ, Xuanwu Hosp, Dept Neurol, Beijing 100053, Peoples R China
Wang, Yuping
[1
,2
]
Hu, Meng
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机构:
Capital Med Univ, Xuanwu Hosp, Dept Neurol, Beijing 100053, Peoples R ChinaCapital Med Univ, Xuanwu Hosp, Dept Neurol, Beijing 100053, Peoples R China
Hu, Meng
[1
]
Han, Xiaosi
论文数: 0引用数: 0
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机构:
Univ Alabama Birmingham, Neurol, Birmingham, AL USACapital Med Univ, Xuanwu Hosp, Dept Neurol, Beijing 100053, Peoples R China
Han, Xiaosi
[4
]
Ding, Qiang
论文数: 0引用数: 0
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机构:
Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USACapital Med Univ, Xuanwu Hosp, Dept Neurol, Beijing 100053, Peoples R China
Ding, Qiang
[3
]
机构:
[1] Capital Med Univ, Xuanwu Hosp, Dept Neurol, Beijing 100053, Peoples R China
[2] Beijing Key Lab Neuromodulat, Beijing, Peoples R China
[3] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA
[4] Univ Alabama Birmingham, Neurol, Birmingham, AL USA
Hypocretin 1 and hypocretin 2 (orexin A and B) regulate sleep, wakefulness and emotion. Tumour necrosis factor alpha (TNF-alpha) is an important neuroinflammation mediator. Here, we examined the effects of TNF-alpha treatment on hypocretin expression in vivo and behaviour in mice. TNF-alpha decreased hypocretin 1 and hypocretin 2 expression in a dose-dependent manner in cultured hypothalamic neurons. TNF-alpha decreased mRNA stability of prepro-hypocretin, the single precursor of hypocretin 1 and hypocretin 2. Mice challenged with TNF-alpha demonstrated decreased expression of prepro-hypocretin, hypocretin 1 and hypocretin 2 in hypothalamus. In response to TNF-alpha, prepro-hypocretin mRNA decay was increased in hypothalamus. TNF-alpha neutralizing antibody restored the expression of prepro-hypocretin, hypocretin 1 and hypocretin 2 in vivo in TNF-alpha challenged mice, supporting hypocretin system can be impaired by increased TNF-alpha through decreasing hypocretin expression. Repeated TNF-alpha challenge induced muscle activity during rapid eye movement sleep and sleep fragmentation, but decreased learning, cognition and memory in mice. TNF-alpha neutralizing antibody blocked the effects of TNF-alpha; in contrast, hypocretin receptor antagonist enhanced the effects of TNF-alpha. The data support that TNF-alpha is involved in the regulation of hypocretin expression, sleep and cognition. The findings shed some lights on the role of neuroinflammation in neurodegenerative diseases including Alzheimer's disease and Parkinson's disease.
机构:
UNIV ADELAIDE,QUEEN ELIZABETH HOSP,DEPT OBSTET & GYNAECOL,REPROD MED UNIT,ADELAIDE,SA,AUSTRALIAUNIV ADELAIDE,QUEEN ELIZABETH HOSP,DEPT OBSTET & GYNAECOL,REPROD MED UNIT,ADELAIDE,SA,AUSTRALIA
Norman, RJ
Milner, C
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机构:
UNIV ADELAIDE,QUEEN ELIZABETH HOSP,DEPT OBSTET & GYNAECOL,REPROD MED UNIT,ADELAIDE,SA,AUSTRALIAUNIV ADELAIDE,QUEEN ELIZABETH HOSP,DEPT OBSTET & GYNAECOL,REPROD MED UNIT,ADELAIDE,SA,AUSTRALIA
Milner, C
Hussey, N
论文数: 0引用数: 0
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机构:
UNIV ADELAIDE,QUEEN ELIZABETH HOSP,DEPT OBSTET & GYNAECOL,REPROD MED UNIT,ADELAIDE,SA,AUSTRALIAUNIV ADELAIDE,QUEEN ELIZABETH HOSP,DEPT OBSTET & GYNAECOL,REPROD MED UNIT,ADELAIDE,SA,AUSTRALIA
Hussey, N
Craig, J
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机构:
UNIV ADELAIDE,QUEEN ELIZABETH HOSP,DEPT OBSTET & GYNAECOL,REPROD MED UNIT,ADELAIDE,SA,AUSTRALIAUNIV ADELAIDE,QUEEN ELIZABETH HOSP,DEPT OBSTET & GYNAECOL,REPROD MED UNIT,ADELAIDE,SA,AUSTRALIA