| First Author | Rahman FU | Year | 2021 |
| Journal | Int J Mol Sci | Volume | 22 |
| Issue | 23 | PubMed ID | 34884616 |
| Mgi Jnum | J:317740 | Mgi Id | MGI:6833577 |
| Doi | 10.3390/ijms222312806 | Citation | Rahman FU, et al. (2021) Topoisomerase IIIbeta Deficiency Induces Neuro-Behavioral Changes and Brain Connectivity Alterations in Mice. Int J Mol Sci 22(23) |
| abstractText | Topoisomerase IIIbeta (Top3beta), the only dual-activity topoisomerase in mammals that can change topology of both DNA and RNA, is known to be associated with neurodevelopment and mental dysfunction in humans. However, there is no report showing clear associations of Top3beta with neuropsychiatric phenotypes in mice. Here, we investigated the effect of Top3beta on neuro-behavior using newly generated Top3beta deficient (Top3beta(-/-)) mice. We found that Top3beta(-/-) mice showed decreased anxiety and depression-like behaviors. The lack of Top3beta was also associated with changes in circadian rhythm. In addition, a clear expression of Top3beta was demonstrated in the central nervous system of mice. Positron emission tomography/computed tomography (PET/CT) analysis revealed significantly altered connectivity between many brain regions in Top3beta(-/-) mice, including the connectivity between the olfactory bulb and the cerebellum, the connectivity between the amygdala and the olfactory bulb, and the connectivity between the globus pallidus and the optic nerve. These connectivity alterations in brain regions are known to be linked to neurodevelopmental as well as psychiatric and behavioral disorders in humans. Therefore, we conclude that Top3beta is essential for normal brain function and behavior in mice and that Top3beta could be an interesting target to study neuropsychiatric disorders in humans. |
