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丛集性头痛预防药物对小鼠下丘脑转录组稳态的影响。

Effects of cluster headache preventatives on mouse hypothalamic transcriptional homeostasis.

机构信息

Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Florence, Italy.

出版信息

Cephalalgia. 2022 Jul;42(8):798-803. doi: 10.1177/03331024221075613. Epub 2022 Feb 15.

Abstract

OBJECTIVE

To investigate how cluster headache preventatives verapamil, lithium and prednisone affect expression of hypothalamic genes involved in chronobiology.

METHODS

C57Bl/6 mice were exposed to daily, oral treatment with verapamil, lithium, prednisone or amitriptyline (as negative control), and transcripts of multiple genes quantified in the anterior, lateral and posterior hypothalamus.

RESULTS

Verapamil, lithium or prednisone did not affect expression of clock genes of the anterior hypothalamus (, , and ). Prednisone altered expression of hypothalamic neuropeptides and within the lateral and posterior hypothalamus, respectively. The three preventatives did not affect expression of the neurohypophyseal hormones and in the posterior hypothalamus. Conversely, amitriptyline reduced mRNA levels of , and

CONCLUSION

Data suggest that cluster headache preventatives act upstream or downstream from the hypothalamus. Our findings provide new insights on hypothalamic homeostasis during cluster headache prophylaxis, as well as neurochemistry underlying cluster headache treatment.

摘要

目的

研究丛集性头痛预防药物维拉帕米、锂和泼尼松如何影响涉及生物钟的下丘脑基因的表达。

方法

将 C57Bl/6 小鼠暴露于每日口服维拉帕米、锂、泼尼松或阿米替林(作为阴性对照),并在下丘脑前、侧和后部定量测定多种基因的转录物。

结果

维拉帕米、锂或泼尼松均不影响下丘脑前区时钟基因(、、和)的表达。泼尼松分别改变了下丘脑神经肽和在侧和后部的表达。这三种预防药物均不影响神经垂体激素和在后丘脑的表达。相反,阿米替林降低了 、和的 mRNA 水平。

结论

数据表明,丛集性头痛预防药物作用于下丘脑的上游或下游。我们的研究结果为丛集性头痛预防期间下丘脑的内稳态以及丛集性头痛治疗的神经化学提供了新的见解。

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