Lack of Astrocytic Glycogen Alters Synaptic Plasticity but Not Seizure Susceptibility
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Lack of Astrocytic Glycogen Alters Synaptic Plasticity but Not Seizure Susceptibility Jordi Duran 1,2 & M. Kathryn Brewer 1 & Arnau Hervera 3,4,5,6 & Agnès Gruart 7 & Jose Antonio del Rio 3,4,5,6 & José M. Delgado-García 7 & Joan J. Guinovart 1,2,8 Received: 17 April 2020 / Accepted: 31 July 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Brain glycogen is mainly stored in astrocytes. However, recent studies both in vitro and in vivo indicate that glycogen also plays important roles in neurons. By conditional deletion of glycogen synthase (GYS1), we previously developed a mouse model entirely devoid of glycogen in the central nervous system (GYS1Nestin-KO). These mice displayed altered electrophysiological properties in the hippocampus and increased susceptibility to kainate-induced seizures. To understand which of these functions are related to astrocytic glycogen, in the present study, we generated a mouse model in which glycogen synthesis is eliminated specifically in astrocytes (GYS1Gfap-KO). Electrophysiological recordings of awake behaving mice revealed alterations in input/ output curves and impaired long-term potentiation, similar, but to a lesser extent, to those obtained with GYS1Nestin-KO mice. Surprisingly, GYS1Gfap-KO mice displayed no change in susceptibility to kainate-induced seizures as determined by fEPSP recordings and video monitoring. These results confirm the importance of astrocytic glycogen in synaptic plasticity. Keywords Glycogen . Long-term potentiation . Plasticity . Epilepsy . Astrocyte . Metabolism
Introduction Most cell types in the body store glucose in the form of glycogen, a branched macromolecule containing up to 55,000 glucose units. The only enzyme able to form glycogen in vivo is glycogen synthase (GYS). There are two isoforms of glycogen synthase in mammals: the muscle isoform, GYS1, which is expressed in all tissues except the liver, and the liver-specific isoform, GYS2. In the brain, glycogen is estimated to comprise about 0.1% of tissue weight [1]. Both
astrocytes and neurons express GYS1 and synthesize glycogen, although glycogen levels in astrocytes are much higher than in neurons [2, 3]. In the past decades, numerous studies have demonstrated that brain glycogen plays a role in memory consolidation and synaptic function (reviewed in [4–6]). In histological studies of the healthy brain, glycogen granules are almost always confined to astrocytic cell bodies and processes [7]. Hence, there is a longstanding belief that the contribution of brain glycogen to cerebral functions is entirely due to its role in
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12035-020-02055-5) contains supplementary material, which is available to authorized users. * Jordi Duran [email protected] 1
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Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, 08028 Barcelona, Spain Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Me
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