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Age-associated reduction of nuclear shape dynamics in excitatory neurons of the visual cortex |
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| Authors: | Tanita Frey Tomonari Murakami Koichiro Maki Takumi Kawaue Naoki Tani Ayaka Sugai Naotaka Nakazawa Kei-ichiro Ishiguro Taiji Adachi Mineko Kengaku Kenichi Ohki Yukiko Gotoh Yusuke Kishi |
| Affiliation: | 1. Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan New York University Grossman School of Medicine, New York, New York, USA;2. Graduate School of Medicine, The University of Tokyo, Tokyo, Japan Institute for AI and Beyond, The University of Tokyo, Tokyo, Japan;3. Institute for Life and Medical Sciences, Kyoto University, Kyoto, Japan;4. Institute for Integrated Cell-Material Sciences, Institute for Advanced Study, Kyoto University, Kyoto, Japan;5. Liaison Laboratory Research Promotion Center, IMEG, Kumamoto University, Kumamoto, Japan;6. Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan Institute for Quantitative Biosciences, The University of Tokyo, Tokyo, Japan;7. Institute for Integrated Cell-Material Sciences, Institute for Advanced Study, Kyoto University, Kyoto, Japan Department of Energy and Materials, Faculty of Science and Engineering, Kindai University, Osaka, Japan;8. Department of Chromosome Biology, Institute of Molecular Embryology and Genetics (IMEG), Kumamoto University, Kumamoto, Japan;9. Graduate School of Medicine, The University of Tokyo, Tokyo, Japan Institute for AI and Beyond, The University of Tokyo, Tokyo, Japan International Research Center for Neurointelligence (WPI-IRCN), The University of Tokyo, Tokyo, Japan;10. Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan International Research Center for Neurointelligence (WPI-IRCN), The University of Tokyo, Tokyo, Japan;11. Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan |
| Abstract: | Neurons decline in their functionality over time, and age-related neuronal alterations are associated with phenotypes of neurodegenerative diseases. In nonneural tissues, an infolded nuclear shape has been proposed as a hallmark of aged cells and neurons with infolded nuclei have also been reported to be associated with neuronal activity. Here, we performed time-lapse imaging in the visual cortex of Nex-Cre;SUN1-GFP mice. Nuclear infolding was observed within 10 min of stimulation in young nuclei, while the aged nuclei were already infolded pre-stimulation and showed reduced dynamics of the morphology. In young nuclei, the depletion of the stimuli restored the nucleus to a spherical shape and reduced the dynamic behavior, suggesting that nuclear infolding is a reversible process. We also found the aged nucleus to be stiffer than the young one, further relating to the age-associated loss of nuclear shape dynamics. We reveal temporal changes in the nuclear shape upon external stimulation and observe that these morphological dynamics decrease with age. |
| Keywords: | aging neuronal activity neurons nuclear shape nuclear stiffness SUN1 visual cortex |