Center for Behavioral Neuroscience, Institute of Experimental Psychology, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
Center for Behavioral Neuroscience, Institute of Experimental Psychology, Heinrich Heine University Düsseldorf, Düsseldorf, Germany; Department of Biomedical Sciences, School of Medicine, University of Minnesota, Duluth, MN, USA.
Pharmacol Biochem Behav. 2019 Apr;179:73-79. doi: 10.1016/j.pbb.2019.02.005. Epub 2019 Feb 16.
In humans, mutations in the Disrupted-in-schizophrenia 1 (DISC1) gene have been related to psychiatric disorders, including symptoms of abnormal cognitive and emotional behaviors. In our previous studies, overexpression of the human DISC1 gene in rats resulted in schizophrenia-like phenotypes showing deficits in motor learning, impaired cognitive function and dysfunctions of the dopamine system. Here we asked, whether the DISC1 overexpression affects locomotor activity in the open field (OF), anxiety in the elevated plus-maze (EPM), depression-related behavior in the forced swim test (FST), and attention-like/short-term working-memory in the spontaneous alternation behavior (SAB) in the T-maze in transgenic DISC1 (tgDISC1) rats and littermate controls (WT). TgDISC1 rats showed enhanced anxiety behavior in the EPM and an impairment in attention-like/short-term working-memory in the SAB. However, tgDISC1 animals showed no locomotor impairments or depression-like behavior in the OF and FST. These results suggest that DISC1 overexpression leads to higher anxiety level and an attention-like/working-memory deficit. These findings may expand the causal role of DISC1 in its contribution to multiple symptom dimensions of psychiatric disorders.
在人类中，精神分裂症相关蛋白 1（DISC1）基因突变与精神疾病有关，包括认知和情绪行为异常的症状。在我们之前的研究中，在大鼠中过表达人 DISC1 基因导致类似精神分裂症的表型，表现为运动学习缺陷、认知功能受损和多巴胺系统功能障碍。在这里，我们询问了过表达 DISC1 是否会影响转基因 DISC1（tgDISC1）大鼠和同窝对照（WT）在旷场（OF）中的运动活动、在高架十字迷宫（EPM）中的焦虑、在强迫游泳试验（FST）中的抑郁相关行为，以及在 T 迷宫中的自发交替行为（SAB）中的注意力样/短期工作记忆。TgDISC1 大鼠在 EPM 中表现出增强的焦虑行为，并且在 SAB 中表现出注意力样/短期工作记忆受损。然而，tgDISC1 动物在 OF 和 FST 中没有运动障碍或抑郁样行为。这些结果表明，DISC1 过表达导致更高的焦虑水平和注意力样/工作记忆缺陷。这些发现可能扩大了 DISC1 在其对精神疾病多种症状维度的贡献中的因果作用。
