Age‐associated reduction of nuclear shape dynamics in excitatory neurons of the visual cortex

Author:

Frey Tanita12,Murakami Tomonari34,Maki Koichiro5ORCID,Kawaue Takumi6,Tani Naoki7,Sugai Ayaka18,Nakazawa Naotaka69,Ishiguro Kei‐ichiro10,Adachi Taiji5ORCID,Kengaku Mineko6,Ohki Kenichi3411,Gotoh Yukiko111,Kishi Yusuke18ORCID

Affiliation:

1. Graduate School of Pharmaceutical Sciences The University of Tokyo Tokyo Japan

2. New York University Grossman School of Medicine New York New York USA

3. Graduate School of Medicine The University of Tokyo Tokyo Japan

4. Institute for AI and Beyond, The University of Tokyo Tokyo Japan

5. Institute for Life and Medical Sciences, Kyoto University Kyoto Japan

6. Institute for Integrated Cell‐Material Sciences, Institute for Advanced Study, Kyoto University Kyoto Japan

7. Liaison Laboratory Research Promotion Center IMEG, Kumamoto University Kumamoto Japan

8. Institute for Quantitative Biosciences, The University of Tokyo Tokyo Japan

9. Department of Energy and Materials, Faculty of Science and Engineering Kindai University Osaka Japan

10. Department of Chromosome Biology Institute of Molecular Embryology and Genetics (IMEG), Kumamoto University Kumamoto Japan

11. International Research Center for Neurointelligence (WPI‐IRCN), The University of Tokyo Tokyo Japan

Abstract

AbstractNeurons 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.

Funder

Japan Agency for Medical Research and Development

Japan Society for the Promotion of Science

Mochida Memorial Foundation for Medical and Pharmaceutical Research

Secom Science and Technology Foundation

Takeda Medical Research Foundation

Publisher

Wiley

Subject

Cell Biology,Aging

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