Repeated psychosocial stress causes glutamic acid decarboxylase isoform-67, oxidative-Nox-2 changes and neuroinflammation in mice: Prevention by treatment with a neuroactive flavonoid, morin
Repeated psychosocial stress causes glutamic acid decarboxylase isoform-67, oxidative-Nox-2 changes and neuroinflammation in mice: Prevention by treatment with a neuroactive flavonoid, morin
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DOI：
10.1016/j.brainres.2020.146917
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发表时间：
2020-10-01
期刊：
影响因子：
2.9
通讯作者：
Iwalewa, Ezekiel O.
中科院分区：
文献类型：
--
作者：
Ben-Azu, Benneth;Emokpae, Osagie;Iwalewa, Ezekiel O.
心理社会压力和生物倾向与精神行为相关的情绪和人格障碍有关。以神经炎症和氧化应激为靶点已被认为是预防心理社会应激所致精神障碍的潜在策略。桑色素是从桑叶中分离出来的一种生物活性化合物，与人参相比，已被证明具有抗记忆、抗精神病和抗炎的作用。人参是一种众所周知的适应原。因此，本研究采用入侵者驻留范式，研究了桑色素对社会挫败应激(SDS)诱导的小鼠行为、神经化学、神经免疫和神经氧化改变的影响。将入侵雄性小鼠随机分为6组(n=10)。第1组(正常对照组)和第2组(SDS对照组)给予生理盐水，第3~5组给予桑色素(25~100 mg/kg)，第6组给予人参(50 mg/kg)，每日1次，连续14天。从第7~14天开始给药30min后，第2~6组分别与攻击性常驻小鼠进行10min的生理对抗和心理对抗。在第14天评估神经行为效应(运动能力、认知能力、焦虑和抑郁样行为)。测定纹状体、前额叶皮质和海马区氧化/氮应激和神经炎症的生物标志物：乙酰胆碱酯酶(AChE)和谷氨酸脱羧酶-67(GAD(67))。桑色素和人参可减轻抑郁所致的行为障碍。桑色素和人参均可降低脑区丙二醛、亚硝酸盐水平，升高谷胱甘肽浓度。它们还能降低炎性介质(肿瘤坏死因子-α、白介素6、环氧合酶-2和核因子-kappaB)、乙酰胆碱酯酶活性和特定脑区NOx-2的表达。然而，与人参相反，桑色素增加了纹状体、前额叶皮质和海马区GAD(67)的水平。我们的结果表明，桑色素通过增强GAD(67)、抑制AChE活性、氧化应激、NOx-2和神经炎症通路来减轻SDS诱导的神经行为缺陷。
Psychosocial stress and biological predispositions are linked to mood and personality disorders related to psychiatric behaviors. Targeting neuroinflammation and oxidative stress has been recognized as a potential strategy for the prevention of psychosocial stress-induced psychiatric disorders. Morin, a bioactive compound isolated from mulberry leaf has been shown to produce antiamnesic, antipsychotic and anti-inflammatory effects relative to ginseng, a well-known adaptogen. Hence, the present study investigated the effect of morin on social-defeat stress (SDS)-induced behavioral, neurochemical, neuroimmune and neurooxidative changes in mice using intruder-resident paradigm. The intruder male mice were distributed into 6 groups (n = 10). Groups 1 (normal-control) and 2 (SDS-control) received normal saline, groups 3-5 had morin (25-100 mg/kg) while group 6 received ginseng (50 mg/kg) intraperitoneally daily for 14 days. Thirty minutes after treatment from days 7-14 onwards, mice in groups 2-6 were exposed to SDS for 10 min physical and psychological confrontations respectively with aggressive-resident mice. Neurobehavioral effects (locomotor activity, cognitive performance, anxiety- and depressive-like behavior) were assessed on day 14. Biomarkers of oxidative/nitrergic stress and neuroinflammation; acetylcholinesterase (AChE) and glutamic-acid decarboxylase-67 (GAD(67)) were measured in the striatum, prefrontal-cortex and hippocampus. Behavioral deficits induced by SDS were attenuated by morin and ginseng. Both morin and ginseng decreased malondialdehyde, nitrite levels and increased glutathione concentrations in the brain regions. They also reduced inflammatory mediators (TNF-alpha, IL-6, COX-2 and NF-kappa B), AChE activity and Nox-2 expression in the specific brain regions. However, morin increased the levels of GAD(67) in the striatum, prefrontal-cortex and hippocampus in contrast to ginseng. Our results suggest that morin mitigates SDS-induced neurobehavioral deficits through enhancement of GAD(67), inhibition of AChE activity, oxidative stress, Nox-2 and neuroinflammatory pathways.