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Neuron-astrocyte metabolic coupling facilitates spinal plasticity and maintenance of inflammatory pain

Long-lasting pain stimuli can trigger maladaptive changes in the spinal cord, reminiscent of plasticity associated with memory formation. Metabolic coupling between astrocytes and neurons has been implicated in neuronal plasticity and memory formation in the central nervous system, but neither its i...

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Main Authors: Marty-Lombardi, Sebastián (Author) , Lu, Shiying (Author) , Ambroziak, Wojciech (Author) , Schrenk-Siemens, Katrin (Author) , Wang, Jialin (Author) , DePaoli-Roach, Anna A. (Author) , Hertle, Anna M. (Author) , Wende, Hagen (Author) , Tappe-Theodor, Anke (Author) , Simonetti, Manuela (Author) , Bading, Hilmar (Author) , Okun, Jürgen G. (Author) , Kuner, Rohini (Author) , Fleming, Thomas (Author) , Siemens, Jan (Author)
Format: Article (Journal)
Language:English
Published: 05 March 2024
In: Nature metabolism
Year: 2024, Pages: 1-20
ISSN:2522-5812
DOI:10.1038/s42255-024-01001-2
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s42255-024-01001-2
Verlag, kostenfrei, Volltext: https://www.nature.com/articles/s42255-024-01001-2
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Author Notes:Sebastián Marty-Lombardi, Shiying Lu, Wojciech Ambroziak, Katrin Schrenk-Siemens, Jialin Wang, Anna A. DePaoli-Roach, Anna M. Hagenston, Hagen Wende, Anke Tappe-Theodor, Manuela Simonetti, Hilmar Bading, Jürgen G. Okun, Rohini Kuner, Thomas Fleming & Jan Siemens
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Summary:Long-lasting pain stimuli can trigger maladaptive changes in the spinal cord, reminiscent of plasticity associated with memory formation. Metabolic coupling between astrocytes and neurons has been implicated in neuronal plasticity and memory formation in the central nervous system, but neither its involvement in pathological pain nor in spinal plasticity has been tested. Here we report a form of neuroglia signalling involving spinal astrocytic glycogen dynamics triggered by persistent noxious stimulation via upregulation of the Protein Targeting to Glycogen (PTG) in spinal astrocytes. PTG drove glycogen build-up in astrocytes, and blunting glycogen accumulation and turnover by Ptg gene deletion reduced pain-related behaviours and promoted faster recovery by shortening pain maintenance in mice. Furthermore, mechanistic analyses revealed that glycogen dynamics is a critically required process for maintenance of pain by facilitating neuronal plasticity in spinal lamina 1 neurons. In summary, our study describes a previously unappreciated mechanism of astrocyte-neuron metabolic communication through glycogen breakdown in the spinal cord that fuels spinal neuron hyperexcitability.
Item Description:Gesehen am 06.03.2024
Physical Description:Online Resource
ISSN:2522-5812
DOI:10.1038/s42255-024-01001-2

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