Research Article, Medicine and Health Sciences, Mental Health and Psychiatry, Schizophrenia, Biology and life sciences, Cell biology, Signal transduction, Cell signaling, CREB signaling, Biology and Life Sciences, Organisms, Eukaryota, Animals, Vertebrates, Amniotes, Mammals, Rodents, Mice, GTPase signaling, Anatomy, Brain, Cerebral Cortex, Cerebellum, Molecular Biology, Molecular Biology Techniques, Molecular Biology Assays and Analysis Techniques, Gene Expression and Vector Techniques, Hyperexpression Techniques, Research and Analysis Methods, Neuroscience, Cognitive Science, Cognitive Neuroscience, Cognitive Neurology, Cognitive Impairment, Neurology, and Hippocampus
Schizophrenia is a psychiatric disorder characterized by positive and negative symptoms and cognitive deficits. The exact cause of schizophrenia is still unknown, but substantial evidence indicates that it has a genetic component. Genome wide association studies demonstrate variants within miR-137 host gene are a risk factor for schizophrenia. However, the direct relationship between the pathophysiology of schizophrenia and the dosage of miR-137 remains unclear. Therefore, in this study, we generated transgenic mice overexpressing miR-137 (miR-137 Tg mice) with the neuron-specific Thy-1 promoter and examined schizophrenia-related phenotypes in these mice. Overexpression of miR-137 was observed in various brain regions of the miR-137 Tg mice, with down-regulation of putative miR-137 targets. MiR-137 Tg mice showed sensory gating deficits in a prepulse inhibition test, social deficits in a sociability and social novelty test, and cognitive deficits in a novel object recognition test. Interestingly, the predicted-altered pathways of the medial prefrontal cortex of miR-137 Tg mice were partially overlapped with those of the dorsolateral prefrontal cortex in postmortem brain of patients who died in equal to or less than 4 years after initial diagnosis of schizophrenia in published data. These results suggest that overexpression of miR-137 in the whole brain induces the several phenotypes that are relevant to aspects of psychiatric disorders, such as schizophrenia. Based on these findings, miR-137 Tg mice may have the potential to become a useful tool in researching the pathophysiology of psychiatric disorders.