Distribution and functional significance of rodent cerebellar glycogen
Akther S, Lee AB, Konno A, Asiminas A, Vittani M, Mishima T, Hirai H, Meehan CF, Duran J, Guinovart J, Ashida H, Morita T, Baba O, Shigemoto R, Nedergaard M, Hirase H. 2026. Distribution and functional significance of rodent cerebellar glycogen. iScience. 29(4), 115192.
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Author
Akther, Sonam;
Lee, Ashley Bomin;
Konno, Ayumu;
Asiminas, Antonis;
Vittani, Marta;
Mishima, Tsuneko;
Hirai, Hirokazu;
Meehan, Claire Francesca;
Duran, Jordi;
Guinovart, Joan;
Ashida, Hitoshi;
Morita, Tsuyoshi
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All
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Abstract
The mammalian brain stores glucose, the main circulating energy substrate, as glycogen. In rodents, the cerebellum contains relatively high glycogen levels, yet its cellular and subcellular distribution remains poorly defined. Using monoclonal antibodies against glycogen, we examined its distribution in the mouse cerebellar cortex. Glycogen was predominantly localized to Bergmann glia (BG) processes in the molecular layer and was also detected in Purkinje cells (PCs), the principal cerebellar neurons. To assess the functional significance of cerebellar glycogen, we analyzed behavior in mice lacking glycogen synthase 1 (Gys1) in BG or PCs using a floxed Gys1 line. Gys1 deficiency in either PCs or GFAP-positive cells reduced anxiety-like behavior, whereas combined deletion caused PC degeneration and ataxia. These findings reveal a critical role for glycogen metabolism in both astrocytes and neurons in cerebellar function.
Publishing Year
Date Published
2026-03-17
Journal Title
iScience
Publisher
Elsevier
Acknowledgement
This work was supported by the Novo Nordisk Foundation (NNFOC0058058, H. Hirase), the Danmarks Frie Forskningsfond (0134-00107B and 5283-00069A, H.Hirase), the Lundbeck Foundation, Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research (KAKENHI) program (22K06454/24H01221, A.K.; 23K27482, H.Hirai), the Japan Agency for Medical Research and Development (AMED) Brain Mapping by Integrated Neurotechnologies for Disease Studies (Brain/MINDS) (JP21dm0207111, H. Hirai), AMED Brain/MINDS 2.0 (JP23wm0625001 and JP24wm0625103, H. Hirai), and grants from the Spanish Ministerio de Ciencia e Innovación (MCIU/FEDER/AEI) (PID2020-118699 GB-100, J.D.) and the Fundación Ramón Areces (J.D.). Sonam Akther has been supported by the RIKEN IPA fellowship. We are thankful to Dr. Yuki Oe for his support in the initial stage of this study and to Dan Xue for his help with the graphical abstract. We thank Dr. Pia Weikop for providing CTN research infrastructure. The authors declare no competing financial interests.
Volume
29
Issue
4
Article Number
115192
eISSN
IST-REx-ID
Cite this
Akther S, Lee AB, Konno A, et al. Distribution and functional significance of rodent cerebellar glycogen. iScience. 2026;29(4). doi:10.1016/j.isci.2026.115192
Akther, S., Lee, A. B., Konno, A., Asiminas, A., Vittani, M., Mishima, T., … Hirase, H. (2026). Distribution and functional significance of rodent cerebellar glycogen. IScience. Elsevier. https://doi.org/10.1016/j.isci.2026.115192
Akther, Sonam, Ashley Bomin Lee, Ayumu Konno, Antonis Asiminas, Marta Vittani, Tsuneko Mishima, Hirokazu Hirai, et al. “Distribution and Functional Significance of Rodent Cerebellar Glycogen.” IScience. Elsevier, 2026. https://doi.org/10.1016/j.isci.2026.115192.
S. Akther et al., “Distribution and functional significance of rodent cerebellar glycogen,” iScience, vol. 29, no. 4. Elsevier, 2026.
Akther S, Lee AB, Konno A, Asiminas A, Vittani M, Mishima T, Hirai H, Meehan CF, Duran J, Guinovart J, Ashida H, Morita T, Baba O, Shigemoto R, Nedergaard M, Hirase H. 2026. Distribution and functional significance of rodent cerebellar glycogen. iScience. 29(4), 115192.
Akther, Sonam, et al. “Distribution and Functional Significance of Rodent Cerebellar Glycogen.” IScience, vol. 29, no. 4, 115192, Elsevier, 2026, doi:10.1016/j.isci.2026.115192.
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