{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T12:42:50Z","timestamp":1789389770348,"version":"build-2803163510"},"reference-count":38,"publisher":"Society for Neuroscience","issue":"14","license":[{"start":{"date-parts":[[2014,10,2]],"date-time":"2014-10-02T00:00:00Z","timestamp":1412208000000},"content-version":"vor","delay-in-days":183,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2014,4,2]]},"abstract":"<jats:p>Oligomerized amyloid-\u03b2 (A\u03b2) peptide is thought to contribute to synaptic damage, resulting in dysfunctional neuronal networks in patients with Alzheimer's disease. It has been previously suggested that A\u03b2 may be detrimental to neuronal health, at least in part, by triggering oxidative\/nitrosative stress. However, the mechanisms underlying this process remain to be elucidated. Here, using rat primary cerebrocortical cultures, we demonstrate that A\u03b2<jats:sub>1\u201342<\/jats:sub>oligomers trigger a dramatic increase in intracellular nitric oxide (NO) concentration via a process mediated by activation of NMDA-type glutamate receptors (NMDARs). Considering that synaptic NMDARs and extrasynaptic NMDARs (eNMDARs) can have opposite effects on neuronal viability, we explored their respective roles in A\u03b2-induced increases in NO levels. Surprisingly, after pharmacological isolation of eNMDARs, we discovered that eNMDARs are primarily responsible for the increase in neuronal NO triggered by A\u03b2 oligomers. Moreover, we found that the eNMDAR-mediated increase in NO can produce S-nitrosylation of Drp1 (dynamin-related protein 1) and Cdk5 (cyclin-dependent kinase 5), targets known to contribute to A\u03b2-induced synaptic damage. These results suggest that pharmacological intervention specifically aimed at eNMDARs may decrease A\u03b2-induced nitrosative stress and thus ameliorate neurotoxic damage to synapses.<\/jats:p>","DOI":"10.1523\/jneurosci.2907-13.2014","type":"journal-article","created":{"date-parts":[[2014,4,2]],"date-time":"2014-04-02T17:22:04Z","timestamp":1396459324000},"page":"5023-5028","source":"Crossref","is-referenced-by-count":60,"title":["Differential Effects of Synaptic and Extrasynaptic NMDA Receptors on A\u03b2-Induced Nitric Oxide Production in Cerebrocortical Neurons"],"prefix":"10.1523","volume":"34","author":[{"given":"Elena","family":"Molokanova","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohd 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