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内源性和外源性 5-羟色胺,而不是舒马曲坦,可改善戊四氮诱导的大鼠癫痫发作模型中的癫痫发作和神经炎症。

Endogenous and exogenous serotonin, but not sumatriptan, ameliorate seizures and neuroinflammation in the pentylenetetrazole-induced seizure model in rats.

机构信息

Bolu Abant Izzet Baysal University, Faculty of Medicine, Department of Physiology, Bolu, Turkey.

Bolu Abant Izzet Baysal University, Faculty of Medicine, Department of Pediatrics, Bolu, Turkey.

出版信息

Arq Neuropsiquiatr. 2022 Jan;80(1):48-55. doi: 10.1590/0004-282X-ANP-2021-0101.

DOI:10.1590/0004-282X-ANP-2021-0101
PMID:35239805
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9651504/
Abstract

BACKGROUND

Epilepsy has neuropsychiatric comorbidities such as depression, bipolar disorder, and anxiety. Drugs that target epilepsy may also be useful for its neuropsychiatric comorbidities.

OBJECTIVE

To investigate the effects of serotonergic modulation on pro-inflammatory cytokines and the seizures in pentylenetetrazole (PTZ)-induced seizure model in rats.

METHODS

Male Wistar rats were injected intraperitoneally with serotonin, selective serotonin reuptake inhibitor fluoxetine, 5-HT1B/D receptor agonist sumatriptan, or saline 30 min prior to PTZ treatment. Behavioral seizures were assessed by the Racine's scale. Concentrations of IL-1β, IL-6, and TNF-α in serum and brain tissue were determined by ELISA.

RESULTS

Serotonin and fluoxetine, but not sumatriptan, alleviated PTZ-induced seizures by prolonging onset times of myoclonic-jerk and generalized tonic-clonic seizures. The anti-seizure effect of fluoxetine was greater than that of serotonin. Likewise, serotonin and fluoxetine, but not sumatriptan, reduced PTZ-induced increases in the levels of IL-1β and IL-6 in both serum and brain tissue. None of the administered drugs including PTZ affected TNF-α concentrations.

CONCLUSIONS

Our findings suggest that endogenous and exogenous serotonin exhibits anticonvulsant effects by suppressing the neuroinflammation. It seems that 5-HT1B/D receptors do not mediate anticonvulsant and anti-neuroinflammatory effects of serotonin.

摘要

背景

癫痫伴有神经精神共病,如抑郁、双相情感障碍和焦虑。针对癫痫的药物可能对其神经精神共病也有效。

目的

研究 5-羟色胺能调制对戊四氮(PTZ)诱导的大鼠癫痫模型中促炎细胞因子和癫痫发作的影响。

方法

雄性 Wistar 大鼠在 PTZ 处理前 30 分钟通过腹腔内注射 5-羟色胺、选择性 5-羟色胺再摄取抑制剂氟西汀、5-HT1B/D 受体激动剂舒马曲坦或生理盐水。通过 Racine 量表评估行为性癫痫发作。通过 ELISA 测定血清和脑组织中 IL-1β、IL-6 和 TNF-α的浓度。

结果

5-羟色胺和氟西汀而非舒马曲坦可通过延长肌阵挛性抽搐和全面强直阵挛性癫痫发作的发作时间来缓解 PTZ 诱导的癫痫发作。氟西汀的抗癫痫作用强于 5-羟色胺。同样,5-羟色胺和氟西汀而非舒马曲坦可降低 PTZ 诱导的血清和脑组织中 IL-1β和 IL-6 水平的升高。给予的药物(包括 PTZ)均未影响 TNF-α浓度。

结论

我们的研究结果表明,内源性和外源性 5-羟色胺通过抑制神经炎症发挥抗惊厥作用。5-HT1B/D 受体似乎不介导 5-羟色胺的抗惊厥和抗神经炎症作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cffa/9651504/acb05c3ebba4/1678-4227-anp-80-01-048-gf03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cffa/9651504/615b95568969/1678-4227-anp-80-01-048-gf01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cffa/9651504/2408bc4f8913/1678-4227-anp-80-01-048-gf02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cffa/9651504/acb05c3ebba4/1678-4227-anp-80-01-048-gf03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cffa/9651504/615b95568969/1678-4227-anp-80-01-048-gf01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cffa/9651504/2408bc4f8913/1678-4227-anp-80-01-048-gf02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cffa/9651504/acb05c3ebba4/1678-4227-anp-80-01-048-gf03.jpg

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