Molecular mechanism of tumour necrosis factor alpha regulates hypocretin (orexin) expression, sleep and behaviour
Molecular mechanism of tumour necrosis factor alpha regulates hypocretin (orexin) expression, sleep and behaviour
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DOI：
10.1111/jcmm.14566
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发表时间：
2019
影响因子：
5.3
通讯作者：
Qiang Ding
中科院分区：
文献类型：
--
作者：
Shuqin Zhan;Pulin Che;Xue‐ke Zhao;Ning Li;Yan Ding;Jianghong Liu;Spring Li;Karyn Ding;Lynn Han;Zhaoyang Huang;Liyong Wu;Yuping Wang;Xiaosi Han;Qiang Ding
Hypocretin 1 and hypocretin 2 (orexin A and B) regulate sleep, wakefulness and.emotion. Tumour necrosis factor alpha (TNF‐α) is an important neuroinflammation.mediator. Here, we examined the effects of TNF‐α treatment on hypocretin.expression in vivo and behaviour in mice. TNF‐α decreased hypocretin 1 and.hypocretin 2 expression in a dose‐dependent manner in cultured hypothalamic.neurons. TNF‐α decreased mRNA stability of prepro‐hypocretin, the single precursor.of hypocretin 1 and hypocretin 2. Mice challenged with TNF‐α demonstrated.decreased expression of prepro‐hypocretin, hypocretin 1 and hypocretin.2 in hypothalamus. In response to TNF‐α, prepro‐hypocretin mRNA decay was.increased in hypothalamus. TNF‐α neutralizing antibody restored the expression.of prepro‐hypocretin, hypocretin 1 and hypocretin 2 in vivo in TNF‐α challenged.mice, supporting hypocretin system can be impaired by increased TNF‐α through.decreasing hypocretin expression. Repeated TNF‐α challenge induced muscle activity.during rapid eye movement sleep and sleep fragmentation, but decreased.learning, cognition and memory in mice. TNF‐α neutralizing antibody blocked.the effects of TNF‐α; in contrast, hypocretin receptor antagonist enhanced the.effects of TNF‐α. The data support that TNF‐α i s i nvolved i n t he r egulation o f.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.
