Distribution and functional significance of rodent cerebellar glycogen

TL;DR

The cerebellum stores glycogen mainly in glial cells and neurons, and disrupting glycogen metabolism leads to neurological issues like ataxia.

Contribution

This study identifies the cellular localization of glycogen in the cerebellum and demonstrates its functional role in neuronal and glial metabolism.

Findings

Glycogen is predominantly found in Bergmann glia processes and Purkinje cells in the cerebellar molecular layer.

Disruption of glycogen synthesis in Purkinje cells or glial cells leads to reduced anxiety-like behavior and cerebellar degeneration.

Combined deletion of glycogen synthase in Purkinje cells and glial cells causes PC degeneration and ataxia.

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.

•Cerebellum contains high amounts of glycogen in the molecular layer•BG and PCs store glycogen in their somata and processes•Interfering PC glycogen synthesis by Gys1 conditional KO reduces BG glycogen•Gys1 KO in PCs and cerebellar GFAP-positive cells induces PC ablation and ataxia

Cerebellum contains high amounts of glycogen in the molecular layer

BG and PCs store glycogen in their somata and processes

Interfering PC glycogen synthesis by Gys1 conditional KO reduces BG glycogen

Gys1 KO in PCs and cerebellar GFAP-positive cells induces PC ablation and ataxia

Molecular neuroscience; Cellular neuroscience

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