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.
Institute for Brain and Intelligence, Southeast University, 2 Sipailou Road, Nanjing, 210096, China.
Nat Commun. 2024 Oct 5;15(1):8639. doi: 10.1038/s41467-024-52974-3.
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 Ca 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.
社交记忆障碍是许多大脑疾病的一个关键症状，但其潜在机制仍不清楚。神经黏附素（NLGs）是细胞黏附分子家族的一员，对突触的发育和功能至关重要，其功能障碍与神经发育和神经精神疾病有关，包括自闭症和精神分裂症。尽管 NLGs 在神经元中得到了广泛研究，但它们在神经胶质细胞中的作用仍知之甚少。在这里，我们发现成年雄性小鼠腹侧海马区的星形胶质细胞中 NLG3 的缺失会损害社交记忆，减弱星形胶质细胞 Ca 信号，增强 EAAT2 的表达，并阻止长时程增强，而这些损伤可以通过增加星形胶质细胞活性、降低 EAAT2 功能或增强腺苷/A2a 受体信号来挽救。这项研究揭示了 NLG3 在星形胶质细胞功能、谷氨酸稳态和社交记忆中的重要作用，并确定了谷氨酸转运体和腺苷信号通路是治疗大脑疾病的潜在治疗策略。
