Pituitary adenylate cyclase-activating polypeptide is associated with schizophrenia
Pituitary adenylate cyclase-activating polypeptide is associated with schizophrenia
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DOI：
10.1038/sj.mp.4001982
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发表时间：
2007-11-01
影响因子：
11
通讯作者：
Baba, A.
中科院分区：
文献类型：
--
作者：
Hashimoto, R.;Hashimoto, H.;Baba, A.
垂体腺苷环化酶激活多肽(PACAP，ADCYAP1)是一种具有神经传递调节活性的神经肽，是一种很有前途的精神分裂症候选基因。在这里，我们提供了编码PACAP及其受体PAC1的基因的遗传变异与精神分裂症相关的证据。我们研究了PACAP基因相关多态对精神分裂症相关神经生物学特征的影响。PACAP基因的这种等位基因在精神分裂症患者中过度表达，与海马体体积减少和记忆能力下降有关。非典型抗精神病药物利培酮可逆转PACAP基因敲除小鼠的异常行为，包括运动活动增加和脉冲前惊厥反应抑制缺陷。这些一致的数据表明，PACAP信号的改变可能参与了精神分裂症的发病机制。
Pituitary adenylate cyclase- activating polypeptide (PACAP, ADCYAP1: adenylate cyclaseactivating polypeptide 1), a neuropeptide with neurotransmission modulating activity, is a promising schizophrenia candidate gene. Here, we provide evidence that genetic variants of the genes encoding PACAP and its receptor, PAC1, are associated with schizophrenia. We studied the effects of the associated polymorphism in the PACAP gene on neurobiological traits related to risk for schizophrenia. This allele of the PACAP gene, which is overrepresented in schizophrenia patients, was associated with reduced hippocampal volume and poorer memory performance. Abnormal behaviors in PACAP knockout mice, including elevated locomotor activity and deficits in prepulse inhibition of the startle response, were reversed by treatment with an atypical antipsychotic, risperidone. These convergent data suggest that alterations in PACAP signaling might contribute to the pathogenesis of schizophrenia.