Akt1 deficiency in schizophrenia and impairment of hippocampal plasticity and function.
Akt1 deficiency in schizophrenia and impairment of hippocampal plasticity and function.
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DOI：
10.1002/hipo.20887
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发表时间：
2012-02
期刊：
影响因子：
3.5
通讯作者：
Lucki, Irwin
中科院分区：
文献类型：
--
作者：
Balu, Darrick T.;Carlson, Gregory C.;Talbot, Konrad;Kazi, Hala;Hill-Smith, Tiffany E.;Easton, Rachel M.;Birnbaum, Morris J.;Lucki, Irwin
遗传学研究已将丝氨酸/苏氨酸激酶Akt1的功能缺陷与精神分裂症联系起来。这种障碍与海马体的发育、结构和功能异常有关，可追溯到Akt1功能异常。为了在Akt1和海马体功能之间建立更紧密的联系，对Akt1选择性缺失的小鼠(Akt1−/−小鼠)进行了检查，以了解依赖于海马体并与精神分裂症相关的生理和行为结果。Akt1的基因缺失与成年出生的海马祖细胞的增殖能力受损和海马长时程增强有关，表明该脑区功能缺陷与神经可塑性有关。此外，Akt1−/−小鼠在情境恐惧条件反射和空间学习回忆方面表现出损害，这些行为已知选择性地涉及海马体。Akt1−/−小鼠也表现出脉冲前对声学惊吓反应的抑制减少，这是一种在精神分裂症中受到干扰的感觉运动门控反应。精神分裂症患者的死后组织样本显示，海马齿状回(海马神经元区)门区神经元中的磷酸化Akt水平显著降低。综上所述，这些结果表明Akt1亚型调节海马神经可塑性和认知，并在精神分裂症的病因中起作用。
Genetic studies have associated deficient function of the serine/threonine kinase Akt1 with schizophrenia. This disorder is associated with developmental, structural, and functional abnormalities of the hippocampus that could be traced to abnormal Akt1 function. To establish a closer connection between Akt1 and hippocampal function, mice with a selective deletion of Akt1 (Akt1−/− mice) were examined for physiological and behavioral outcomes dependent on the hippocampus and associated with schizophrenia. Genetic deletion of Akt1 was associated with both impaired proliferative capacity of adult-born hippocampal progenitors and hippocampal long-term potentiation, indicating deficient functions of this brain region associated with neuroplasticity. Moreover, Akt1−/− mice demonstrated impairments in contextual fear conditioning and recall of spatial learning, behaviors known to selectively involve the hippocampus. Akt1−/− mice also showed reduced prepulse inhibition of the acoustic startle response, a sensorimotor gating response that is perturbed in schizophrenia. Postmortem tissue samples from patients with schizophrenia showed significant reductions of phosphorylated Akt levels in hilar neurons of the dentate gyrus, the neurogenic zone of the hippocampus. Taken together, these results implicate the Akt1 isoform in regulating hippocampal neuroplasticity and cognition and in contributing to the etiology of schizophrenia.
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DOI：
10.1002/ajmg.b.30291
发表时间：
2006-06-05
影响因子：
2.8
作者：
Bajestan, Sepideh N.;Sabouri, Amir H.;Osame, Mitsubiro
通讯作者：
Osame, Mitsubiro
影响因子：
30.8
作者：
Emamian, ES;Hall, D;Gogos, JA
通讯作者：
Gogos, JA
影响因子：
8.2
作者：
Balu, Darrick T.;Lucki, Irwin
通讯作者：
Lucki, Irwin
影响因子：
3.9
作者：
Dummler, B.;Hemmings, B. A.
通讯作者：
Hemmings, B. A.
影响因子：
4.7
作者：
Ide, Masayuki;Ohnishi, Tetsuo;Yoshikawa, Takeo
通讯作者：
Yoshikawa, Takeo