The anthraquinone derivative Emodin ameliorates neurobehavioral deficits of a rodent model for schizophrenia
The anthraquinone derivative Emodin ameliorates neurobehavioral deficits of a rodent model for schizophrenia
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DOI：
10.1007/s00702-007-0867-5
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发表时间：
2008-03-01
影响因子：
3.3
通讯作者：
Nawa, H.
中科院分区：
文献类型：
--
作者：
Mizuno, M.;Kawamura, H.;Nawa, H.
细胞因子信号传导的异常与精神分裂症的神经病理学有关。以前，我们建立了一个动物模型，精神分裂症的表皮生长因子（EGF）的新生大鼠。在这里，我们研究了蒽醌衍生物大黄素（3-甲基-1，6，8-三羟基蒽醌）和番泻苷（双-[D-吡喃葡萄糖基-氧基]-四氢-4，4 '-二羟基-二氧代[联蒽]-2，2'-二羧酸）对该模型和EGF信号传导行为的影响。亚慢性口服大黄素（50 mg/kg）抑制声惊吓反应，消除前脉冲抑制（PPI）的赤字在这个啮齿动物模型。协方差分析显示大黄素对PPI和惊吓反应有明显的影响。相反，番泻苷（50 mg/kg）没有影响。大黄素衰减体重增加最初在治疗过程中，但没有明显的影响体重增加和自发活动之后。应用大黄素的新皮层文化衰减ErbB 1和ErbB 2的磷酸化。我们的结论是，大黄素可以减弱EGF受体信号转导和改善行为缺陷。因此，大黄素可能是一类新型的抗精神病药物的前药。
Abnormality in cytokine signaling is implicated in the neuropathology of schizophrenia. Previously, we established an animal model for schizophrenia by administering epidermal growth factor (EGF) to neonatal rats. Here we investigated effects of the anthraquinone derivatives emodin (3-methyl-1,6,8-trihydroxyanthraquinone) and sennoside (bis-[D-glucopyranosyl-oxy]-tetrahydro-4,4'-dihydroxy-dioxo[bianthracene]-2,2'-dicarboxylic acid) on behaviors of this model and EGF signaling. Subchronic oral administration of emodin (50 mg/kg) suppressed acoustic startle responses and abolished prepulse inhibition (PPI) deficits in this rodent model. ANCOVA revealed that emodin had distinct effects on PPI and startle responses. In contrast, sennoside (50 mg/kg) had no effects. Emodin attenuated weight gain initially during treatment but had no apparent effect on weight gain and locomotor activity thereafter. Application of emodin to neocortical cultures attenuated the phosphorylation of ErbB1 and ErbB2. We conclude that emodin can both attenuate EGF receptor signaling and ameliorate behavioral deficits. Therefore, emodin might be a novel class of a pro-drug for anti-psychotic medication.