Ketogenic diet-induced peroxisome proliferator-activated receptor-γ activation decreases neuroinflammation in the mouse hippocampus after kainic acid-induced seizures
Ketogenic diet-induced peroxisome proliferator-activated receptor-γ activation decreases neuroinflammation in the mouse hippocampus after kainic acid-induced seizures
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DOI：
10.1016/j.expneurol.2011.09.001
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发表时间：
2011-12-01
影响因子：
5.3
通讯作者：
Roh, Gu Seob
中科院分区：
文献类型：
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作者：
Jeong, Eun Ae;Jeon, Byeong Tak;Roh, Gu Seob
与禁食类似，生酮饮食（KD）具有抗炎作用，并防止兴奋性毒性介导的神经元细胞死亡。最近的研究表明，过氧化物酶体增殖物激活受体（PPAR）γ在癫痫发作动物模型中具有抗炎作用。然而，KD抗炎作用的确切机制尚未确定。在这里，我们研究了KD和乙酰乙酸（AA）对癫痫发作动物模型和谷氨酸处理的HT 22细胞中神经炎症的影响。给小鼠喂食MD 4周，并在MA注射后2或6 h处死。在KA处理后2 h，MD降低海马肿瘤坏死因子α（TNF-α）水平和核因子（NF）-κ B（B）易位到核中。通过蛋白质印迹和免疫荧光评估，KA降低了神经元中MD诱导的PPAR γ激活。最后，KD抑制环氧合酶（考克斯）-2和微粒体前列腺素E-2合酶-1（mPGES-1）在海马表达后6小时MA处理。AA处理还通过降低TNF-α和PPAR γ介导的考克斯-2表达来保护HT 22细胞免受谷氨酸诱导的细胞死亡。因此，KD可以通过KD或AA激活PPAR γ抑制考克斯-2依赖性途径来抑制神经炎症。(C)2011 Elsevier Inc. All rights reserved.
Similar to fasting, the ketogenic diet (KD) has anti-inflammatory effects and protects against excitotoxicity-mediated neuronal cell death. Recent studies have shown that peroxisome proliferator-activated receptor (PPAR)gamma has anti-inflammatory effects in seizure animal models. However, the exact mechanisms underlying the anti-inflammatory effects of the KD have not been determined for seizures. Here we investigated the effect of the KD and acetoacetate (AA) on neuroinflammation in a seizure animal model and glutamate-treated HT22 cells, respectively. Mice were fed the MD for 4 weeks and sacrificed 2 or 6 h after MA injection. The MD reduced hippocampal tumor necrosis factor alpha (TNF-alpha) levels and nuclear factor (NF)-kappa B translocation into the nucleus 2 h after KA treatment. MD-induced PPAR gamma activation was decreased by KA in neurons as assessed by western blotting and immunofluorescence. Finally, the KD inhibited cyclooxygenase (COX)-2 and microsomal prostaglandin E-2 synthase-1 (mPGES-1) expression in the hippocampus 6 h after MA treatment. AA treatment also protected against glutamate-induced cell death in HT22 cells by reducing TNF-alpha and PPAR gamma-mediated COX-2 expression. Thus, the KD may inhibit neuroinflammation by suppressing a COX-2-dependent pathway via activation of PPAR gamma by the KD or AA. (C) 2011 Elsevier Inc. All rights reserved.