Antiepileptic and Neuroprotective Biochemical Actions of Sabinene Prevent the Development of Pentylenetetrazol-Induced Seizures and Neuropsychiatric Comorbidities in Mice

IF 2.7 4区 医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Grant Alumona, Benneth Ben-Azu, Daniel T. Esuku, Bienose S. Chijioke, Akhator J. Amenotie, Ayereoghene S. Moses, Faith B. Friday, Emuesiri G. Moke, Obukohwo M. Oyovwi, Ekpekuro Abo, Abayomi M. Ajayi
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引用次数: 0

Abstract

Epilepsy is a long-term neurological disorder that leads to disability with neuropsychiatric comorbidities. Studies have shown that neurochemical imbalances involved in the disease are linked to heightened oxidative and inflammatory pathways, which significantly affect the severity of the disease. As a result, substances that have antioxidant and anti-inflammatory effects might help in managing the condition. Hence, this study investigated the effects of sabinene, a natural monoterpene in essential oils, against pentylenetetrazol-induced seizure kindling and neuropsychiatric comorbidities in mice, revealing insights into the neurochemical, antioxidant, and anti-inflammatory biochemical mechanisms involved. Male Swiss mice in adulthood were pretreated with sabinene (5 and 10 mg/kg) or diazepam (3 mg/kg) 30 min prior to pentylenetetrazol-induced seizures, with injections administered every other day for 28 days. We conducted behavioral assessments using a Racine scale (0–6) and evaluated comorbidities such as cognitive impairments and depression. Neurochemical, antioxidant and anti-inflammatory biochemical mechanisms of the antiepileptic effect of sabinene against pentylenetetrazol-induced kindling were analyzed in the prefrontal cortex and hippocampus, two brain regions largely involved in the disease’s onset and development. Sabinene inhibits pentylenetetrazol-induced seizures evidenced by the reduced frequency and severity of seizure episodes. Sabinene decreases motor activity, reverses pentylenetetrazol-associated spatial/non-spatial memory deficits, increases sociability, and lowers the depressive symptoms. These behavioral changes reversed by sabinene were accompanied by reduced prefrontal-hippocampal glutamate release and increase GAD enzyme. Consistent with this, sabinene elevated IL-10 in both brain areas while also increasing the levels of prefrontal pro-inflammatory cytokines, such as TNF-α and IL-1β. However, sabinene reduced TNF-α and IL-1β in the hippocampus, as well as oxidant markers (malondialdehyde, nitrite), and increased antioxidant systems in both brain regions compared to the pentylenetetrazol cohorts. Overall, sabinene’s antiepileptic and neuroprotective effects include modulating neurotransmitter imbalances, inhibiting oxidative stress, and modulating cortical neuroimmune dysfunction.

Abstract Image

Abstract Image

沙宾烯的抗癫痫和神经保护生化作用预防戊四唑诱导的小鼠癫痫发作和神经精神合并症的发生
癫痫是一种长期的神经系统疾病,可导致伴有神经精神合并症的残疾。研究表明,与该疾病相关的神经化学失衡与氧化和炎症途径的增加有关,这显著影响了疾病的严重程度。因此,具有抗氧化和抗炎作用的物质可能有助于控制这种情况。因此,本研究调查了sabinene(精油中的天然单萜)对戊四唑诱导的癫痫发作和小鼠神经精神合并症的影响,揭示了其中的神经化学、抗氧化和抗炎生化机制。成年雄性瑞士小鼠在戊四唑诱发癫痫发作前30分钟预先注射沙宾烯(5和10 mg/kg)或地西泮(3 mg/kg),每隔一天注射一次,持续28天。我们使用拉辛量表(0-6)进行行为评估,并评估合并症,如认知障碍和抑郁。在前额叶皮质和海马这两个主要参与疾病发生和发展的大脑区域,分析了sabinene抗戊四唑诱导的抗癫痫作用的神经化学、抗氧化和抗炎生化机制。Sabinene抑制戊四唑诱导的癫痫发作,癫痫发作的频率和严重程度降低。Sabinene减少运动活动,逆转戊四唑相关的空间/非空间记忆缺陷,增加社交能力,减轻抑郁症状。sabinene逆转了这些行为变化,并伴有前额叶-海马谷氨酸释放减少和GAD酶增加。与此一致的是,sabinene升高了两个脑区的IL-10,同时也增加了前额叶促炎细胞因子(如TNF-α和IL-1β)的水平。然而,与戊四氮组相比,sabinene降低了海马中的TNF-α和IL-1β,以及氧化标志物(丙二醛,亚硝酸盐),并增加了两个大脑区域的抗氧化系统。总的来说,sabinene的抗癫痫和神经保护作用包括调节神经递质失衡,抑制氧化应激,调节皮质神经免疫功能障碍。
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来源期刊
Journal of Molecular Neuroscience
Journal of Molecular Neuroscience 医学-神经科学
CiteScore
6.60
自引率
3.20%
发文量
142
审稿时长
1 months
期刊介绍: The Journal of Molecular Neuroscience is committed to the rapid publication of original findings that increase our understanding of the molecular structure, function, and development of the nervous system. The criteria for acceptance of manuscripts will be scientific excellence, originality, and relevance to the field of molecular neuroscience. Manuscripts with clinical relevance are especially encouraged since the journal seeks to provide a means for accelerating the progression of basic research findings toward clinical utilization. All experiments described in the Journal of Molecular Neuroscience that involve the use of animal or human subjects must have been approved by the appropriate institutional review committee and conform to accepted ethical standards.
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