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Disruption of the astrocyte–neuron interaction is responsible for the impairments in learning and memory in 5XFAD mice: an Alzheimers disease animal model

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Authors
Choi, Moonseok; Lee, Sang-Min; Kim, Dongsoo; Im, Heh-In; Kim, Hye-Sun; Jeong, Yun Ha
Issue Date
2021-07-10
Publisher
BMC
Citation
Molecular Brain. 2021 Jul 10;14(1):111
Keywords
Astrocyte–neuron interactionLearning impairmentsMemory impairmentsAlzheimer’s disease, 5XFAD mice
Abstract
The morphological dynamics of astrocytes are altered in the hippocampus during memory induction. Astrocyte–neuron interactions on synapses are called tripartite synapses. These control the synaptic function in the central nervous system. Astrocytes are activated in a reactive state by STAT3 phosphorylation in 5XFAD mice, an Alzheimers disease (AD) animal model. However, changes in astrocyte–neuron interactions in reactive or resting-state astrocytes during memory induction remain to be defined. Here, we investigated the time-dependent changes in astrocyte morphology and the number of astrocyte–neuron interactions in the hippocampus over the course of long-term memory formation in 5XFAD mice. Hippocampal-dependent long-term memory was induced using a contextual fear conditioning test in 5XFAD mice. The number of astrocytic processes increased in both wild-type and 5XFAD mice during memory formation. To assess astrocyte–neuron interactions in the hippocampal dentate gyrus, we counted the colocalization of glial fibrillary acidic protein and postsynaptic density protein 95 via immunofluorescence. Both groups revealed an increase in astrocyte–neuron interactions after memory induction. At 24 h after memory formation, the number of tripartite synapses returned to baseline levels in both groups. However, the total number of astrocyte–neuron interactions was significantly decreased in 5XFAD mice. Administration of Stattic, a STAT3 phosphorylation inhibitor, rescued the number of astrocyte–neuron interactions in 5XFAD mice. In conclusion, we suggest that a decreased number of astrocyte–neuron interactions may underlie memory impairment in the early stages of AD.
ISSN
1756-6606
Language
English
URI
https://hdl.handle.net/10371/174814
DOI
https://doi.org/10.1186/s13041-021-00823-5
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College of Medicine/School of Medicine (의과대학/대학원)Neuroscience (뇌신경과학전공)Journal Papers (저널논문_뇌신경과학전공)
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