TY - JOUR
T1 - Lack of Astrocytic Glycogen Alters Synaptic Plasticity but Not Seizure Susceptibility
AU - Duran, Jordi
AU - Brewer, M. Kathryn
AU - Hervera, Arnau
AU - Gruart, Agnès
AU - del Rio, Jose Antonio
AU - Delgado-García, José M.
AU - Guinovart, Joan J.
N1 - Funding Information:
This study was supported by grants from the MINECO (BFU2017-82375-R to AG and JMD-G, RTI2018-099773-B-I00 to JADR and AH, and BFU2017-84345-P to JD and JG), the CIBER de Diabetes y Enfermedades Metabólicas Asociadas (ISCIII, Ministerio de Ciencia e Innovación), and a grant from the National Institutes of Health (NIH NINDS P01NS097197) to JG. The project also received funding from “la Caixa” Foundation (ID 100010434) under the agreement LCF/PR/HR19/52160007 with JADR. MKB has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No. 754510. Acknowledgments
Publisher Copyright:
© 2020, Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2020/11/1
Y1 - 2020/11/1
N2 - 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.
AB - 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.
KW - Astrocyte
KW - Epilepsy
KW - Glycogen
KW - Long-term potentiation
KW - Metabolism
KW - Plasticity
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UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=pure_univeritat_ramon_llull&SrcAuth=WosAPI&KeyUT=WOS:000557320600002&DestLinkType=FullRecord&DestApp=WOS_CPL
U2 - 10.1007/s12035-020-02055-5
DO - 10.1007/s12035-020-02055-5
M3 - Article
C2 - 32770452
AN - SCOPUS:85089086942
SN - 0893-7648
VL - 57
SP - 4657
EP - 4666
JO - Molecular Neurobiology
JF - Molecular Neurobiology
IS - 11
ER -