Fernanda Kulinski Mello, Tuane Bazanella Sampaio, Bruna Neuberger, Michele Pereira Mallmann, Michele Rechia Fighera, Luiz Fernando Freire Royes, Ana Flávia Furian, James W Larrick, Mauro Schneider Oliveira
{"title":"癫痫状态后鼻内注射 Na+、K+-ATP 酶激活抗体的脑电图和行为效应","authors":"Fernanda Kulinski Mello, Tuane Bazanella Sampaio, Bruna Neuberger, Michele Pereira Mallmann, Michele Rechia Fighera, Luiz Fernando Freire Royes, Ana Flávia Furian, James W Larrick, Mauro Schneider Oliveira","doi":"10.1021/acschemneuro.4c00141","DOIUrl":null,"url":null,"abstract":"<p><p>Status epilepticus (SE) is a medical emergency associated with high mortality and morbidity. Na<sup>+</sup>, K<sup>+</sup>-ATPase, is a promising therapeutic target for SE, given its critical role in regulation of neuron excitability and cellular homeostasis. We investigated the effects of a Na<sup>+</sup>, K<sup>+</sup>-ATPase-activating antibody (DRRSAb) on short-term electrophysiological and behavioral consequences of pilocarpine-induced SE. Rats were submitted to pilocarpine-induced SE, followed by intranasal administration (2 μg/nostril). The antibody increased EEG activity following SE, namely, EEG power in theta, beta, and gamma frequency bands, assessed by quantitative analysis of EEG power spectra. One week later, DRRSAb-treated animals displayed less behavioral hyperreactivity in pick-up tests and better performance in novel object recognition tests, indicating that the intranasal administration of this Na<sup>+</sup>, K<sup>+</sup>-ATPase activator immediately after SE improves behavioral outcomes at a later time point. These results suggest that Na<sup>+</sup>, K<sup>+</sup>-ATPase activation warrants further investigation as an adjunctive therapeutic strategy for SE.</p>","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":null,"pages":null},"PeriodicalIF":4.1000,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11311123/pdf/","citationCount":"0","resultStr":"{\"title\":\"Electroencephalographic and Behavioral Effects of Intranasal Administration of a Na<sup>+</sup>, K<sup>+</sup>-ATPase-Activating Antibody after Status Epilepticus.\",\"authors\":\"Fernanda Kulinski Mello, Tuane Bazanella Sampaio, Bruna Neuberger, Michele Pereira Mallmann, Michele Rechia Fighera, Luiz Fernando Freire Royes, Ana Flávia Furian, James W Larrick, Mauro Schneider Oliveira\",\"doi\":\"10.1021/acschemneuro.4c00141\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Status epilepticus (SE) is a medical emergency associated with high mortality and morbidity. Na<sup>+</sup>, K<sup>+</sup>-ATPase, is a promising therapeutic target for SE, given its critical role in regulation of neuron excitability and cellular homeostasis. We investigated the effects of a Na<sup>+</sup>, K<sup>+</sup>-ATPase-activating antibody (DRRSAb) on short-term electrophysiological and behavioral consequences of pilocarpine-induced SE. Rats were submitted to pilocarpine-induced SE, followed by intranasal administration (2 μg/nostril). The antibody increased EEG activity following SE, namely, EEG power in theta, beta, and gamma frequency bands, assessed by quantitative analysis of EEG power spectra. One week later, DRRSAb-treated animals displayed less behavioral hyperreactivity in pick-up tests and better performance in novel object recognition tests, indicating that the intranasal administration of this Na<sup>+</sup>, K<sup>+</sup>-ATPase activator immediately after SE improves behavioral outcomes at a later time point. These results suggest that Na<sup>+</sup>, K<sup>+</sup>-ATPase activation warrants further investigation as an adjunctive therapeutic strategy for SE.</p>\",\"PeriodicalId\":13,\"journal\":{\"name\":\"ACS Chemical Neuroscience\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.1000,\"publicationDate\":\"2024-08-07\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11311123/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"ACS Chemical Neuroscience\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1021/acschemneuro.4c00141\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/7/11 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Chemical Neuroscience","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1021/acschemneuro.4c00141","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/7/11 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
癫痫状态(SE)是一种与高死亡率和高发病率相关的医疗急症。鉴于 Na+、K+-ATPase 在调节神经元兴奋性和细胞稳态中的关键作用,它是治疗癫痫状态的一个很有前景的靶点。我们研究了Na+、K+-ATP酶激活抗体(DRRSAb)对皮质类固醇诱导的SE的短期电生理和行为后果的影响。对大鼠进行皮洛卡品诱导的 SE,然后鼻内给药(2 μg/nostril)。通过对脑电图功率谱的定量分析,该抗体增加了SE后的脑电图活动,即θ、β和γ频段的脑电图功率。一周后,DRRSAb处理过的动物在拾物测试中表现出较低的行为过度反应,在新物体识别测试中表现更好,这表明在SE后立即鼻内注射这种Na+、K+-ATP酶激活剂可改善后期的行为结果。这些结果表明,Na+、K+-ATPase 激活作为 SE 的辅助治疗策略值得进一步研究。
Electroencephalographic and Behavioral Effects of Intranasal Administration of a Na+, K+-ATPase-Activating Antibody after Status Epilepticus.
Status epilepticus (SE) is a medical emergency associated with high mortality and morbidity. Na+, K+-ATPase, is a promising therapeutic target for SE, given its critical role in regulation of neuron excitability and cellular homeostasis. We investigated the effects of a Na+, K+-ATPase-activating antibody (DRRSAb) on short-term electrophysiological and behavioral consequences of pilocarpine-induced SE. Rats were submitted to pilocarpine-induced SE, followed by intranasal administration (2 μg/nostril). The antibody increased EEG activity following SE, namely, EEG power in theta, beta, and gamma frequency bands, assessed by quantitative analysis of EEG power spectra. One week later, DRRSAb-treated animals displayed less behavioral hyperreactivity in pick-up tests and better performance in novel object recognition tests, indicating that the intranasal administration of this Na+, K+-ATPase activator immediately after SE improves behavioral outcomes at a later time point. These results suggest that Na+, K+-ATPase activation warrants further investigation as an adjunctive therapeutic strategy for SE.
期刊介绍:
ACS Chemical Neuroscience publishes high-quality research articles and reviews that showcase chemical, quantitative biological, biophysical and bioengineering approaches to the understanding of the nervous system and to the development of new treatments for neurological disorders. Research in the journal focuses on aspects of chemical neurobiology and bio-neurochemistry such as the following:
Neurotransmitters and receptors
Neuropharmaceuticals and therapeutics
Neural development—Plasticity, and degeneration
Chemical, physical, and computational methods in neuroscience
Neuronal diseases—basis, detection, and treatment
Mechanism of aging, learning, memory and behavior
Pain and sensory processing
Neurotoxins
Neuroscience-inspired bioengineering
Development of methods in chemical neurobiology
Neuroimaging agents and technologies
Animal models for central nervous system diseases
Behavioral research