{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T18:57:09Z","timestamp":1790621829362,"version":"4.1.0"},"reference-count":47,"publisher":"SAGE Publications","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2022,1,4]]},"abstract":"<jats:p>Background: Soluble oligomeric amyloid-\u03b2 (A\u03b2)-induced synaptic dysfunction is an early event in Alzheimer\u2019s disease (AD) pathogenesis. Mounting evidence has suggested N-methyl-D-aspartate receptors (NMDARs) play an important role in A\u03b2-induced synaptotoxicity. Originally NMDARs were believed to be expressed exclusively in neurons; however, recent two decades studies have demonstrated functional NMDARs present on astrocytes. Neuronal NMDARs are modulators of neurodegeneration, while our previous initial study found that astrocytic NMDARs mediated synaptoprotection and identified nerve growth factor (NGF) secreted by astrocytes, as a likely mediator, but how astrocytic NMDARs protect neurons against A\u03b2-induced synaptotoxicity through regulating NGF remains unclear. Objective: To achieve further insight into the mechanism of astrocytic NMDARs oppose A\u03b2-induced synaptotoxicity through regulating NGF. Methods: With the primary hippocampal neuronal and astrocytic co-cultures, astrocytes were pretreated with agonist or antagonist of NMDARs before A\u03b2142 oligomers application to neuron-astrocyte co-cultures. Western blot, RT-PCR, etc., were used for the related proteins evaluation. Results: Activation of astrocytic NMDARs can significantly mitigate A\u03b2142-induced loss of PSD-95 and synaptophysin through increasing NGF release. Blockade of astrocytic NMDARs inhibited A\u03b2-induced compensatory protective NGF increase in protein and mRNA levels through modulating NF-\u03baB of astrocytes. Astrocytic NMDARs activation can enhance A\u03b2-induced Furin increase, and blockade of astrocytic NMDARs inhibited A\u03b2-induced immunofluorescent intensity elevation of vesicle trafficking protein VAMP3 and NGF double-staining. Conclusion: Astrocytic NMDARs oppose A\u03b2-induced synaptotoxicity through modulating the synthesis, maturation, and secretion of NGF in astrocytes. This new information may contribute to the quest for specific targeted strategy of intervention to delay the onset of AD.<\/jats:p>","DOI":"10.3233\/jad-210730","type":"journal-article","created":{"date-parts":[[2021,11,12]],"date-time":"2021-11-12T11:08:53Z","timestamp":1636715333000},"page":"167-178","source":"Crossref","is-referenced-by-count":9,"title":["Astrocytic N-Methyl-D-Aspartate Receptors Protect the Hippocampal Neurons Against Amyloid-\u03b2142-Induced Synaptotoxicity by Regulating Nerve Growth Factor"],"prefix":"10.1177","volume":"85","author":[{"given":"Yizhi","family":"Song","sequence":"first","affiliation":[{"name":"Department of Anatomy, School of Basic Medical Sciences, Beijing Key Laboratory of Neural Regeneration and Repair, Beijing Institute of Brain Disorders, Capital Medical University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zunshu","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Anatomy, School 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