Long-term potentiation-based screening identifies neuronal PYGM as a synaptic plasticity regulator participating in Alzheimer’s disease

Ting Wang; Yun-Qiang Zhou; Yong Wang; Liang Zhang; Xiang Zhu; Xiu-Yan Wang; Jing-Hui Wang; Lin-Kun Han; Jian Meng; Xian Zhang; Hong Luo; Qi-Lin Ma; Zhan-Xiang Wang; Yun-Wu Zhang

doi:10.24272/j.issn.2095-8137.2023.123

Volume 44 Issue 5

Sep. 2023

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Article Navigation > Zoological Research > 2023 > 44(5): 867-881

Ting Wang, Yun-Qiang Zhou, Yong Wang, Liang Zhang, Xiang Zhu, Xiu-Yan Wang, Jing-Hui Wang, Lin-Kun Han, Jian Meng, Xian Zhang, Hong Luo, Qi-Lin Ma, Zhan-Xiang Wang, Yun-Wu Zhang. Long-term potentiation-based screening identifies neuronal PYGM as a synaptic plasticity regulator participating in Alzheimer’s disease. Zoological Research, 2023, 44(5): 867-881. doi: 10.24272/j.issn.2095-8137.2023.123

Citation:

Ting Wang, Yun-Qiang Zhou, Yong Wang, Liang Zhang, Xiang Zhu, Xiu-Yan Wang, Jing-Hui Wang, Lin-Kun Han, Jian Meng, Xian Zhang, Hong Luo, Qi-Lin Ma, Zhan-Xiang Wang, Yun-Wu Zhang. Long-term potentiation-based screening identifies neuronal PYGM as a synaptic plasticity regulator participating in Alzheimer’s disease. Zoological Research, 2023, 44(5): 867-881. doi: 10.24272/j.issn.2095-8137.2023.123

Citation:

Ting Wang, Yun-Qiang Zhou, Yong Wang, Liang Zhang, Xiang Zhu, Xiu-Yan Wang, Jing-Hui Wang, Lin-Kun Han, Jian Meng, Xian Zhang, Hong Luo, Qi-Lin Ma, Zhan-Xiang Wang, Yun-Wu Zhang. Long-term potentiation-based screening identifies neuronal PYGM as a synaptic plasticity regulator participating in Alzheimer’s disease. Zoological Research, 2023, 44(5): 867-881. doi: 10.24272/j.issn.2095-8137.2023.123

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Long-term potentiation-based screening identifies neuronal PYGM as a synaptic plasticity regulator participating in Alzheimer’s disease

doi: 10.24272/j.issn.2095-8137.2023.123

1.
Xiamen Key Laboratory of Brain Center, The First Affiliated Hospital of Xiamen University, and Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, School of Medicine, Xiamen University, Xiamen, Fujian 361102, China
2.
Fujian Provincial Clinical Research Center for Brain Diseases, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian 361003, China

RNA-seq data were deposited into the Sequence Archive of the China National GeneBank Database (Chen et al., 2020; Guo et al., 2020b) with accession number CNP0003942, Sequence Read Archive of the National Center for Biotechnology Information with accession number PRJNA972124, and Genome Sequence Archive of the China National Center for Bioinformation with accession number CRA011030. These data were also submitted to the ZR Journal Community portal at https://www.scidb.cn/c/zoores with a Data DOI of 10.57760/sciencedb.08216.
Supplementary data to this article can be found online.
The authors declare that they have no competing interests.
T.W. carried out most electrophysiological, biochemical, and animal behavioral studies. Y.Q.Z., Y.W., L.Z., Xiang Z., and X.Y.W. helped with animal work. J.H.W. helped with electrophysiological analysis. L.K.H. and J.M. helped with biochemical studies. Xian Z. and H.L. provided technical support. Q.L.M. and Z.X.W. provided intellectual contributions. Y.W.Z. conceived and supervised the project. T.W. and Y.W.Z. wrote the manuscript. All authors reviewed the manuscript. All authors read and approved the final version of the manuscript.

Funds: This work was supported by the National Natural Science Foundation of China (U21A20361 and 82130039 to Y.W.Z.), Fundamental Research Funds for the Central Universities (20720220133 to Y.W.Z.), Natural Science Foundation of Fujian Province (2021J02057 to Q.L.M.), Science and Technology Plan Projects of Fujian Province (2020Y2015 to Z.X.W.), and 2020 Joint Support of Key Projects on Health Care (3502Z20209005 to Z.X.W.)

More Information

Corresponding author: E-mail: yunzhang@xmu.edu.cn
Received Date: 2023-04-07
Accepted Date: 2023-08-02

Published Online: 2023-08-03

Publish Date: 2023-09-18

Abstract

Abstract

Synaptic dysfunction is an important pathological hallmark and cause of Alzheimer’s disease (AD). High-frequency stimulation (HFS)-induced long-term potentiation (LTP) has been widely used to study synaptic plasticity, with impaired LTP found to be associated with AD. However, the exact molecular mechanism underlying synaptic plasticity has yet to be completely elucidated. Whether genes regulating synaptic plasticity are altered in AD and contribute to disease onset also remains unclear. Herein, we induced LTP in the hippocampal CA1 region of wild-type (WT) and AD model mice by administering HFS to the CA3 region and then studied transcriptome changes in the CA1 region. We identified 89 genes that may participate in normal synaptic plasticity by screening HFS-induced differentially expressed genes (DEGs) in mice with normal LTP, and 43 genes that may contribute to synaptic dysfunction in AD by comparing HFS-induced DEGs in mice with normal LTP and AD mice with impaired LTP. We further refined the 43 genes down to 14 by screening for genes with altered expression in pathological-stage AD mice without HFS induction. Among them, we found that the expression of Pygm, which catabolizes glycogen, was also decreased in AD patients. We further demonstrated that down-regulation of PYGM in neurons impaired synaptic plasticity and cognition in WT mice, while its overexpression attenuated synaptic dysfunction and cognitive deficits in AD mice. Moreover, we showed that PYGM directly regulated energy generation in neurons. Our study not only indicates that PYGM-mediated energy production in neurons plays an important role in synaptic function, but also provides a novel LTP-based strategy to systematically identify genes regulating synaptic plasticity under physiological and pathological conditions.
- Alzheimer’s disease,
- High-frequency stimulation,
- Long-term potentiation,
- PYGM,
- Synaptic plasticity,
- Transcriptome

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References(50)

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