Abstract
Neuropsychiatric disorders have a high incidence worldwide. Kinesins, a family of microtubule-based molecular motor proteins, play essential roles in intracellular and axonal transport. Variants of kinesins have been found to be related to many diseases, including neurodevelopmental/neurodegenerative disorders. Kinesin-12 (also known as Kif15) was previously found to affect the frequency of both directional microtubule transports. However, whether Kif15 deficiency impacts mood in mice is yet to be investigated. In this study, we used the CRISPR/Cas9 method to obtain Kif15−/− mice. In behavioral tests, Kif15−/− female mice exhibited prominent depressive characteristics. Further studies showed that the expression of BDNF was significantly decreased in the frontal cortex, corpus callosum, and hippocampus of Kif15−/− mice, along with the upregulation of Interleukin-6 and Interleukin-1β in the corpus callosum. In addition, the expression patterns of AnkG were notably changed in the developing brain of Kif15−/− mice. Based on our previous studies, we suggested that this appearance of altered AnkG was due to the maladjustment of the microtubule patterns induced by Kif15 deficiency. The distribution of PSD95 in neurites notably decreased after cultured neurons treated with the Kif15 inhibitor, but total PSD95 protein level was not impacted, which revealed that Kif15 may contribute to PSD95 transportation. This study suggested that Kif15 may serve as a potential target for future depression studies.
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The data that support the findings of this study are available on reasonable request from the corresponding author.
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Acknowledgements
The authors would like to thank Dr. Dandan Chu for the constructive help in animal behavior detection.
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This work was supported by grants from the National Natural Science Foundation of China (32070725, 31171007).
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Junpei Wang: Conceptualization, Investigation, and Writing– original draft; Qifeng Tu: Investigation; Siming Zhang: Investigation; Xiaomei He: Investigation; Xiaowei Qian: Investigation; Chao Ma: Investigation; Ronghua Wu: Investigation, Resources; Xinyu Shi: Investigation; Zhangyi Yang: Investigation, Yan Liu: Resource, Funding acquisition; Zhangji Dong: Visualization, Writing—Review & Editing; Mei Liu: Conceptualization, Project administration, Funding acquisition, Writing—Review & Editing.
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Wang, J., Tu, Q., Zhang, S. et al. Kif15 deficiency contributes to depression-like behavior in mice. Metab Brain Dis 38, 2369–2381 (2023). https://doi.org/10.1007/s11011-023-01238-y
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DOI: https://doi.org/10.1007/s11011-023-01238-y