@entity2388 Dehydrogenase Kinase-Mediated Glycolytic Metabolic Shift in the Dorsal Root Ganglion Drives XXXX .

@entity33314 @entity6 @entity63 @entity19 @entity26 @entity3839 @entity3949 @entity72784 @entity56 @entity880 @entity158 @entity209 @entity4854 @entity413 @entity2388
UNASSIGNED: The dorsal root ganglion (DRG) is a highly vulnerable site in @entity3949 . Under @entity6 conditions, the DRG experiences tissue @entity63 or lower ambient @entity26 tension that leads to aberrant metabolic functions. @entity209 have been documented to play a crucial role in the pathogenesis of diverse @entity158 @entity56 . However, the contribution of @entity6 -induced @entity209 in the DRG to the pathogenesis of @entity3949 remains ill-explored. In this study, we report that @entity2388 dehydrogenase kinases ( @entity72784 and @entity33314 ), key regulatory enzymes in @entity413 metabolism, mediate glycolytic metabolic shift in the DRG leading to @entity3949 . @entity3839 -induced @entity6 substantially enhanced the expression and activity of the PDKs in the DRG, and the genetic ablation of @entity72784 and @entity33314 attenuated the @entity4854 -induced @entity158 . Mechanistically, @entity72784 /4 deficiency inhibited the @entity6 -induced lactate surge, expression of @entity158 -related ion channels, activation of satellite glial cells, and infiltration of macrophages in the DRG, in addition to reducing central sensitization and neuroinflammation hallmarks in the spinal cord, which likely accounts for the attenuated @entity158 . @entity72784 /4-deficient @entity19 were partly resistant to the @entity6 -induced loss of peripheral nerve structure and function. Furthermore, in the experiments using DRG neuron cultures, @entity880 treatment enhanced the expression of the ion channels and compromised cell viability. Finally, the pharmacological inhibition of DRG PDKs or @entity880 production substantially attenuated @entity6 -induced @entity158 . Taken together, @entity72784 /4 induction and the subsequent @entity880 surge induce the metabolic shift in the @entity6 DRG, thereby contributing to the pathogenesis of @entity3949 .
