Florey Institute of Neuroscience and Mental Health, University of Melbourne, Australia.
Department of Anatomy and Neuroscience, University of Melbourne, Australia.
Prog Neuropsychopharmacol Biol Psychiatry. 2015 Jan 2;56:247-53. doi: 10.1016/j.pnpbp.2014.09.009. Epub 2014 Oct 5.
Alterations in immune function have been implicated in the aetiopathogenesis of schizophrenia. Specifically, the induction of inflammatory cytokines, which are important immunological factors in infection or inflammation, may be critical factors altering the normal course of brain development and increasing schizophrenia risk. Suppressor of cytokine signalling 2 (SOCS2) can negatively regulate the signalling of cytokines. The present study aimed to determine the behavioural phenotype of transgenic mice over-expressing SOCS2 (SOCS2 Tg) in paradigms of relevance to schizophrenia. Both male and female SOCS2 Tg mice displayed reduced locomotor hyperactivity after the administration of the dopamine releaser, amphetamine, compared to wildtype controls (WT). However, only male SOCS2 Tg mice showed enhanced prepulse inhibition compared to WT. Dopamine D2 receptors mRNA expression was reduced and dopamine transporter mRNA expression was increased in the nucleus accumbens of female, but not male, SOCS2 Tg mice, compared to WT. The role of hyperdopaminergia has long been implicated in the aetiology of schizophrenia. This study shows that over-expression of SOCS2 reduces the psychostimulant effects of amphetamine, enhances PPI, and alters mesolimbic dopaminergic activity. SOCS2 may provide a novel target in the development of treatments for schizophrenia.
免疫功能的改变与精神分裂症的病因发病机制有关。具体来说，诱导炎症细胞因子的产生，这些细胞因子是感染或炎症中重要的免疫因素，可能是改变正常大脑发育过程并增加精神分裂症风险的关键因素。细胞因子信号转导抑制因子 2（SOCS2）可以负向调节细胞因子的信号转导。本研究旨在确定过表达 SOCS2（SOCS2 Tg）的转基因小鼠在与精神分裂症相关的范式中的行为表型。与野生型对照（WT）相比，雄性和雌性 SOCS2 Tg 小鼠在给予多巴胺释放剂安非他命后表现出运动过度兴奋减少。然而，只有雄性 SOCS2 Tg 小鼠表现出与 WT 相比增强的前脉冲抑制。与 WT 相比，雌性 SOCS2 Tg 小鼠的伏隔核中多巴胺 D2 受体 mRNA 表达减少，多巴胺转运体 mRNA 表达增加，但雄性 SOCS2 Tg 小鼠则没有。多巴胺能亢进在精神分裂症的病因学中一直被认为是一个重要因素。本研究表明，SOCS2 的过表达减少了安非他命的精神兴奋剂作用，增强了 PPI，并改变了中脑边缘多巴胺能活性。SOCS2 可能为精神分裂症的治疗提供新的靶点。
