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首页> 外文期刊>BMC Neuroscience >Prototypical antipsychotic drugs protect hippocampal neuronal cultures against cell death induced by growth medium deprivation
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Prototypical antipsychotic drugs protect hippocampal neuronal cultures against cell death induced by growth medium deprivation

机译：典型的抗精神病药可保护海马神经元培养物免受生长培养基剥夺诱导的细胞死亡

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Background Several clinical studies suggested that antipsychotic-based medications could ameliorate cognitive functions impaired in certain schizophrenic patients. Accordingly, we investigated the effects of various dopaminergic receptor antagonists – including atypical antipsychotics that are prescribed for the treatment of schizophrenia – in a model of toxicity using cultured hippocampal neurons, the hippocampus being a region of particular relevance to cognition. Results Hippocampal cell death induced by deprivation of growth medium constituents was strongly blocked by drugs including antipsychotics (10-10-10-6 M) that display nM affinities for D2 and/or D4 receptors (clozapine, haloperidol, (±)-sulpiride, domperidone, clozapine, risperidone, chlorpromazine, (+)-butaclamol and L-741,742). These effects were shared by some caspases inhibitors and were not accompanied by inhibition of reactive oxygen species. In contrast, (-)-raclopride and remoxipride, two drugs that preferentially bind D2 over D4 receptors were ineffective, as well as the selective D3 receptor antagonist U 99194. Interestingly, (-)-raclopride (10-6 M) was able to block the neuroprotective effect of the atypical antipsychotic clozapine (10-6 M). Conclusion Taken together, these data suggest that D2-like receptors, particularly the D4 subtype, mediate the neuroprotective effects of antipsychotic drugs possibly through a ROS-independent, caspase-dependent mechanism.
机译：背景多项临床研究表明，基于抗精神病药的药物可改善某些精神分裂症患者受损的认知功能。因此，在使用培养的海马神经元的毒性模型中，我们研究了各种多巴胺能受体拮抗剂（包括为治疗精神分裂症开出的非典型抗精神病药）的作用，海马是与认知特别相关的区域。结果剥夺生长培养基成分所致的海马细胞死亡被抗精神病药（10 -10 -10 -6 M）强烈阻断，这些药物对D sub具有nM亲和力> 2 和/或D 4 受体（氯氮平，氟哌啶醇，（±）-舒必利，多潘立酮，氯氮平，利培酮，氯丙嗪，（+）-丁ac醇和L-741742）。这些作用被某些胱天蛋白酶抑制剂所共有，并且不伴有活性氧的抑制。相比之下，与D 4 受体相比优先结合D 2 的两种药物（-）-雷氯必利和雷莫昔必定以及选择性D 3 < / sub>受体拮抗剂U99194。有趣的是，（-）-雷氯必利（10 -6 M）能够阻断非典型抗精神病药物氯氮平（10 -6 M）。结论综上所述，这些数据表明D2样受体，特别是D 4 亚型，可能通过ROS依赖性，caspase依赖性机制介导抗精神病药物的神经保护作用。

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