Topoisomerase IIIβ deficiency induces neuro-behavioral changes and brain connectivity alterations in mice

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Title
Topoisomerase IIIβ deficiency induces neuro-behavioral changes and brain connectivity alterations in mice
Author(s)
F U Rahman; You-Rim Kim; Eun-kyeung KimHae Rim KimSang Mi ChoJin Soo Lee; S J Kim; K Araki; K Yamamura; Mi Ni Lee; Seul Gi Park; Won Kee YoonKihoon LeeYoung Suk WonHyoung-Chin Kim; Y Lee; H Y Lee; Ki Hoan Nam
Bibliographic Citation
International Journal of Molecular Sciences, vol. 22, no. 23, pp. 12806-12806
Publication Year
2021
Abstract
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.
Keyword
Top3βBrain connectivityBehavioral impairmentsAnxietyDepressionCircadian activityNeuropsychiatric disorders
ISSN
1661-6596
Publisher
MDPI
DOI
http://dx.doi.org/10.3390/ijms222312806
Type
Article
Appears in Collections:
Ochang Branch Institute > Division of Bioinfrastructure > Laboratory Animal Resource Center > 1. Journal Articles
Ochang Branch Institute > Division of Bioinfrastructure > 1. Journal Articles
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