前頭前皮質でのTenenrin-4減少による新規双極性障害モデルマウスの作成

抄録

Bipolar disorder (BD) is a disease with reiterate depressive and manic states. In the genome-wide association studies, Single nucleotide polymorphisms of ODZ4 were reported in BD patients. However, the function of Teneurin-4, the protein encoded by ODZ4 gene, in the brain is unclear. In the present study, we investigated whether reduction of Teneurin-4 expression in the prefrontal cortex (PFC) exhibits bipolar-like behavior in mice. Specific knockdown of Teneurin-4 to PFC was achieved by bilateral injection of CRISPER/Cas9 adeno-associated virus vectors. Four weeks after injection, we performed behavioral experiments to evaluated depressive symptoms. The expression of Teneurin-4 in the PFC of these mice (miTenm4 mice) was decreased to 70.8±8.2% compared to control group (100±9.1%). In miTenm4 mice, the immobility time in tail suspension was increased to 164.7±7.1 sec compared to control mice (130.1±15.6 sec), and that in forced swimming test was increased to 218.7±6.9 sec compared to control mice (179.2±12.1 sec). To evaluated the manic symptoms of miTenm4 mice, a long-term running wheel test was performed. As a result, the number of rotations of miTenm4 mice had a tendency to increase compared to control mice. These results suggest that reduction of Teneurin-4 in PFC induced depressive, and manic behaviors.