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焦虑特征对匹鲁卡品癫痫模型的行为及免疫组织学结果产生影响。

Anxious Profile Influences Behavioral and Immunohistological Findings in the Pilocarpine Model of Epilepsy.

作者信息

Kohek Silvia Regina Bica, Foresti Maira Licia, Blanco Miriam Marcela, Cavarsan Clarissa Fantin, da Silva Clivandir Severino, Mello Luiz E

机构信息

Physiology Department, Universidade Federal de São Paulo, São Paulo, Brazil.

Instituto D' Or de Pesquisa e Ensino, Rio de Janeiro, Brazil.

出版信息

Front Pharmacol. 2021 Apr 30;12:640715. doi: 10.3389/fphar.2021.640715. eCollection 2021.

Abstract

Anxiety and epilepsy have a complex bidirectional relationship, where a depressive/anxious condition is a factor that can trigger seizures which in turn can aggravate the depressive/anxious condition. In addition, brain structures such as the hippocampus and amygdala might have a critical relevance in both epilepsy and anxiety. The aim of the present work was to investigate the influence of different anxious profiles to epileptogenesis. Initially, animals were screened through the elevated plus-maze anxiety test, and then seizure development was evaluated using the pilocarpine model of epilepsy. There were no differences in the susceptibility to status epilepticus, mortality rate or frequency of spontaneous recurrent seizures between animals characterized as anxious as compared to the non-anxious animals. Next, we evaluated immunohistological patterns related to seizures and anxiety in various related brain areas. Despite a decrease in the density of neuropeptide Y and parvalbumin expression in epileptic animals, those presenting greater neuropeptide Y immunoreactivity in various brain regions, also showed higher spontaneous recurrent seizures frequency. Differences on the anxious profile showed to interfere with some of these findings in some regions. In addition, animals that were injected with pilocarpine, but did not develop status epilepticus, had behavioral and neuroanatomical alterations as compared to control animals, indicating its importance as an additional tool for investigating the heterogeneity of the epileptogenic response after an initial insult. This study allowed to better understand the association between anxiety and temporal lobe epilepsy and might allow for therapeutic targets to be developed to minimize the negative impacts associated with it.

摘要

焦虑与癫痫存在复杂的双向关系,抑郁/焦虑状态是引发癫痫发作的一个因素,而癫痫发作反过来又会加重抑郁/焦虑状态。此外,海马体和杏仁核等脑结构在癫痫和焦虑中可能都具有关键意义。本研究的目的是调查不同焦虑状态对癫痫发生的影响。最初,通过高架十字迷宫焦虑试验对动物进行筛选,然后使用匹罗卡品癫痫模型评估癫痫发作的发展情况。与非焦虑动物相比,被判定为焦虑的动物在癫痫持续状态的易感性、死亡率或自发性复发性癫痫发作频率方面没有差异。接下来,我们评估了各个相关脑区与癫痫发作和焦虑相关的免疫组织学模式。尽管癫痫动物中神经肽Y和小清蛋白表达密度降低,但在各个脑区神经肽Y免疫反应性较高的动物,其自发性复发性癫痫发作频率也较高。焦虑状态的差异显示会在某些区域干扰其中一些研究结果。此外,注射了匹罗卡品但未出现癫痫持续状态的动物,与对照动物相比存在行为和神经解剖学改变,这表明其作为研究初次损伤后癫痫发生反应异质性的额外工具具有重要性。这项研究有助于更好地理解焦虑与颞叶癫痫之间的关联,并可能有助于开发治疗靶点以尽量减少与之相关的负面影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4c4/8132119/7fbcfc3a7089/fphar-12-640715-g001.jpg

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