2. Academic Validation
  3. Astrocytic neuroligin 3 regulates social memory and synaptic plasticity through adenosine signaling in male mice

Astrocytic neuroligin 3 regulates social memory and synaptic plasticity through adenosine signaling in male mice

  • Nat Commun. 2024 Oct 5;15(1):8639. doi: 10.1038/s41467-024-52974-3.
Rui Dang # 1 2 3 4,  An Liu # 5 6 7 8,  Yu Zhou 1 2 3,  Xingcan Li 1 2,  Miao Wu 1 2,  Kun Cao 1 2,  Yanghong Meng 9 10,  Haiwang Zhang 9 10,  Guangming Gan 11,  Wei Xie 12 13 14,  Zhengping Jia 15 16
Affiliations

Affiliations

  • 1 The Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, The School of Life Science and Technology, Southeast University, 2 Sipailou Road, Nanjing, 210096, China.
  • 2 Institute for Brain and Intelligence, Southeast University, 2 Sipailou Road, Nanjing, 210096, China.
  • 3 Shenzhen Research Institute, Southeast University, 19 Gaoxin South 4th Road, Shenzhen, 518063, China.
  • 4 Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ, 08854, USA.
  • 5 The Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, The School of Life Science and Technology, Southeast University, 2 Sipailou Road, Nanjing, 210096, China. liu_an@seu.edu.cn.
  • 6 Institute for Brain and Intelligence, Southeast University, 2 Sipailou Road, Nanjing, 210096, China. liu_an@seu.edu.cn.
  • 7 Shenzhen Research Institute, Southeast University, 19 Gaoxin South 4th Road, Shenzhen, 518063, China. liu_an@seu.edu.cn.
  • 8 Neurosciences & Mental Health, The Hospital for Sick Children, 555 University Ave., Toronto, ON, M5G 1X8, Canada. liu_an@seu.edu.cn.
  • 9 Neurosciences & Mental Health, The Hospital for Sick Children, 555 University Ave., Toronto, ON, M5G 1X8, Canada.
  • 10 Department of Physiology, Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada.
  • 11 School of Medicine, Southeast University, Nanjing, Jiangsu, 210009, China.
  • 12 The Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, The School of Life Science and Technology, Southeast University, 2 Sipailou Road, Nanjing, 210096, China. wei.xie@seu.edu.cn.
  • 13 Institute for Brain and Intelligence, Southeast University, 2 Sipailou Road, Nanjing, 210096, China. wei.xie@seu.edu.cn.
  • 14 Jiangsu Co-innovation Center of Neuroregeneration, Southeast University, 2 Sipailou Road, Nanjing, 210096, China. wei.xie@seu.edu.cn.
  • 15 Neurosciences & Mental Health, The Hospital for Sick Children, 555 University Ave., Toronto, ON, M5G 1X8, Canada. zhengping.jia@sickkids.ca.
  • 16 Department of Physiology, Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada. zhengping.jia@sickkids.ca.
  • # Contributed equally.
PMID: 39366972 DOI: 10.1038/s41467-024-52974-3
Abstract

Social memory impairment is a key symptom of many brain disorders, but its underlying mechanisms remain unclear. Neuroligins (NLGs) are a family of cell adhesion molecules essential for synapse development and function and their dysfunctions are linked to neurodevelopmental and neuropsychiatric disorders, including autism and schizophrenia. Although NLGs are extensively studied in neurons, their role in glial cells is poorly understood. Here we show that astrocytic deletion of NLG3 in the ventral hippocampus of adult male mice impairs social memory, attenuates astrocytic CA2+ signals, enhances the expression of EAAT2 and prevents long-term potentiation, and these impairments are rescued by increasing astrocyte activity, reducing EAAT2 function or enhancing adenosine/A2a receptor signaling. This study has revealed an important role of NLG3 in astrocyte function, glutamate homeostasis and social memory and identified the glutamate transporter and adenosine signaling pathway as potential therapeutic strategies to treat brain disorders.

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