マウス海馬における Teneurin-4 発現減少によるうつ様行動の誘導

抄録

Numbers of patients with mental disorders have been significantly increased in the worldwide. A single nucleotide polymorphism of Odz4 of bipolar disorder patients had been reported in Genome Wide Association Study. Odz4 encodes Teneurin-4 (Tenm4). Therefore, we investigated the physiological role of Tenm4 by knocking down Tenm4 specifically in the hippocampus (Hip). The Hip is considered to be a region that is involved in mental disorders, as there are reports that the volume of the Hip shrinks in patients with depression and bipolar disorder, and that the neurons of the Hip from bipolar disorder patients show excessive excitation. In this study, we examined the effects of hippocampal-specific knockdown of Tenm4 on behavioral phenotypes using a genetic modification technique applying the CRISPR-Cas9 system. gRNA vector (knock downed Tenm4; Tenm4KD mice) or control vector (mock mice) were injected into the dorsal Hip of C57BL/6J mice. At 4 weeks after the injection, various behavioral experiments were conducted. Tenm4KD mice had no effect on locomotor activity, novel object recognition or working memory, social or anxiety-like behaviors. However, the immobility time of Tenm4KD mice (264.7 ± 10.5 sec) increased compared with mock mice (241.4 ± 4.0 sec) in the forced swimming test, and the sucrose preference of Tenm4KD mice (80.0 ± 2.5%) decreased compared with mock mice (87.6 ± 1.5%). These results suggest that knockdown Tenm4 in the mice Hip exhibited depression-like behavior. We will continue our research to clarify the depressive mechanisms.