感觉运动门控缺陷和抗精神病药对 VGF 过表达小鼠过度活动的影响。
Sensorimotor gating deficits and effects of antipsychotics on the hyperactivity in VGF-overexpressing mice.
机构信息
Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan.
Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan.
出版信息
Pharmacol Rep. 2018 Jun;70(3):476-480. doi: 10.1016/j.pharep.2017.11.013. Epub 2017 Nov 22.
BACKGROUND
VGF nerve growth factor inducible (VGF) is a neuropeptide which is expressed in neuronal cells and endocrine cells. VGF is induced by several neurotrophic factors. The expression level of VGF in patients with schizophrenia is increased in cerebrospinal fluid (CSF) and prefrontal cortex. In our previous study, we generated mice in which the expression level of VGF in the brain was increased. VGF-overexpressing mice exhibited abnormal behaviors including hyperactivity. However, it remains unknown whether VGF-overexpressing mice exhibit the endophenotype of schizophrenia and whether abnormal behaviors in these mice can be improved by antipsychotics.
METHODS
In the present study, we investigated schizophrenia-like behaviors and the responsiveness to antipsychotics in transgenic mice.
RESULTS
VGF-overexpressing mice (1) exhibited prepulse inhibition (PPI) impairment, (2) showed normalized hyperactivity following antipsychotic drug treatment, and (3) showed abnormal responsiveness to haloperidol.
CONCLUSION
Upregulation of VGF may be implicated in the pathophysiology of schizophrenia and abnormalities of dopaminergic signaling.
背景
神经生长因子诱导的 VGF（VGF nerve growth factor inducible）是一种在神经元细胞和内分泌细胞中表达的神经肽。VGF 可被多种神经营养因子诱导。精神分裂症患者脑脊液（CSF）和前额叶皮层中 VGF 的表达水平升高。在我们之前的研究中，我们生成了大脑中 VGF 表达水平升高的小鼠。VGF 过表达小鼠表现出异常行为，包括多动。然而，目前尚不清楚 VGF 过表达小鼠是否表现出精神分裂症的内表型，以及这些小鼠的异常行为是否可以通过抗精神病药物改善。
方法
在本研究中，我们研究了转基因小鼠的精神分裂样行为和对抗精神病药物的反应。
结果
VGF 过表达小鼠（1）表现出前脉冲抑制（PPI）损伤，（2）在抗精神病药物治疗后表现出正常的多动，（3）对氟哌啶醇的反应异常。
结论
VGF 的上调可能与精神分裂症的病理生理学和多巴胺能信号的异常有关。
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