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- W2061861243 abstract "Evidence implicates serotonergic input to spinal dorsal horn neurons in shifting the NMDA receptor (NMDAR) into a high functional output profile after spinal nerve ligation (SNL). We investigated the involvement of adaptor protein NADH dehydrogenase subunit 2 (ND2) in NMDAR-phosphorylation and spinal hyperexcitability secondary to peripheral nerve injury. Immunofluorescence for ND2 was found in dorsal horn neurons immunopositive for NMDAR subunit NR1. Co-localization of ND2 with postsynaptic marker PSD-95 was significantly increased 60min after SNL (Rr 0.77 vs Rr 0.06 in sham controls; z=-242.85; p<0.01 at Fisher's exact test). Western blot analyses confirmed ND2 up-regulation both in cytoplasmic (S2) and synaptic (P3) compartments (p<0.01 at the Student's t test). SNL was followed by increased co-localization of ND2 with the phosphorylated form (serine 896) of NR1 (pNMDA). Spinal superfusion with ND2 inhibitor rotenone prevented up-regulation of ND2 (Rr 0.06 after rotenone vs Rr 0.78 in vehicle-treated controls, z=-253.22, p<0.01) and pNR1 in P3. C fiber-evoked dorsal horn field potentials were increased 60min after SNL by superfusion with NMDA agonist cis-ACPD at 100nM (p<0.01 at the Bonferroni test), however cis-ACPD was effective only at 10μM following prior administration of rotenone. Rotenone also abolished enhancement of evoked potentials induced by simultaneous stimulation of NMDA and 5-HR2B receptors in uninjured rats. Increased postsynaptic up-regulation of ND2/pNMDAR 60min after SNL was prevented by prior administration of selective 5-HT2B antagonist SB204741. These results support a pivotal role for ND2 in coupling serotonergic input to NMDAR-activation during neuropathic pain." @default.
- W2061861243 created "2016-06-24" @default.
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- W2061861243 creator A5068747252 @default.
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- W2061861243 date "2014-05-01" @default.
- W2061861243 modified "2023-10-16" @default.
- W2061861243 title "Coupling of serotonergic input to NMDA receptor-phosphorylation following peripheral nerve injury via rapid, synaptic up-regulation of ND2" @default.
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- W2061861243 doi "https://doi.org/10.1016/j.expneurol.2014.02.014" @default.
- W2061861243 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/24560713" @default.
- W2061861243 hasPublicationYear "2014" @default.
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