ArticleNeurochemical research2026
Thalamic PDK-PDHA1 Signaling is Associated with Opioid-Induced Loss-of-Righting-Reflex Sensitivity: Evidence from Phosphoproteomic Profiling and PDK Pathway Intervention.
Article in Neurochemical research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Opioids are widely used in clinical sedation and anesthesia, but the downstream phosphorylation events associated with opioid-induced reductions in arousal remain incompletely understood. Here, we investigated whether thalamic phosphoproteomic remodeling and the pyruvate dehydrogenase kinase (PDK)-pyruvate dehydrogenase E1 alpha subunit (PDHA1) pathway are associated with opioid-induced loss of righting reflex (LORR) in rats. Phosphoproteomic profiling of rat thalamic tissues after treatment with fentanyl, FENT-001 (a synthetic fentanyl analog), and other sedative and anesthetic agents revealed broad changes in thalamic phosphopeptide abundance.Differentially phosphorylated proteins were enriched in neuronal projections, synapses, cytoskeletal organization and synaptic transmission. PDHA1 was identified as a significantly differentially phosphorylated protein and was further examined by Western blotting. Fentanyl and 3-methylfentanyl altered phosphorylation at multiple PDHA1 sites. Pharmacological inhibition of PDKs with dichloroacetate reduced PDHA1 Ser293 phosphorylation in cultured cortical neurons and produced numerical increases in the estimated ED
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