Topoisomerase IIIβ Deficiency Induces Neuro-Behavioral Changes and Brain Connectivity Alterations in Mice
| Autor: | Young Hee Lee, Eun-Kyeung Kim, Chin-Soo Lee, Ki-Hoan Nam, Won-Kee Yoon, Young-Suk Won, Hyoung-Chin Kim, Sang-Mi Cho, You-Rim Kim, Hae-Rim Kim, Ki Hoon Lee, Faiz Ur Rahman, Seul Gi Park, Ken Ichi Yamamura, Mi-Ni Lee, Kimi Araki, Su Jin Kim, Ho-Young Lee |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
Cerebellum QH301-705.5 Central nervous system Amygdala Catalysis Article Inorganic Chemistry Mice medicine Connectome Animals circadian activity Circadian rhythm Physical and Theoretical Chemistry Biology (General) Molecular Biology QD1-999 Spectroscopy Mice Knockout Top3β brain connectivity behavioral impairments anxiety depression neuropsychiatric disorders Mice Inbred ICR biology Behavior Animal Topoisomerase Organic Chemistry General Medicine Anxiety Disorders Computer Science Applications Olfactory bulb Circadian Rhythm Mice Inbred C57BL Chemistry medicine.anatomical_structure Globus pallidus DNA Topoisomerases Type I biology.protein Optic nerve Female Neuroscience |
| Zdroj: | International Journal of Molecular Sciences, Vol 22, Iss 12806, p 12806 (2021) International Journal of Molecular Sciences; Volume 22; Issue 23; Pages: 12806 International Journal of Molecular Sciences |
| ISSN: | 1661-6596 1422-0067 |
| Popis: | Topoisomerase IIIβ (Top3β), 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 Top3β with neuropsychiatric phenotypes in mice. Here, we investigated the effect of Top3β on neuro-behavior using newly generated Top3β deficient (Top3β−/−) mice. We found that Top3β−/− mice showed decreased anxiety and depression-like behaviors. The lack of Top3β was also associated with changes in circadian rhythm. In addition, a clear expression of Top3β 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 Top3β−/− 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 Top3β is essential for normal brain function and behavior in mice and that Top3β could be an interesting target to study neuropsychiatric disorders in humans. |
| Databáze: | OpenAIRE |
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