Modulation of pain sensitivity by Ascl1- and Lhx6-dependent GABAergic neuronal function in streptozotocin diabetic mice

• DOI: 10.1016/j.ymthe.2024.12.039
• Publication Date: 2024-12-30T17:11:27Z
• Authors: Sung-Min Hwang; Md. Mahbubur Rahman; Eun Jin Go; Jueun Roh; Rayoung Park; Sung-Gwon Lee; Minyeop Nahm; Temugin Berta; Yong Ho Kim; Chul-Kyu Park
• Keywords: Modulation (music)

Painful diabetic neuropathy commonly affects the peripheral nervous system in individuals with diabetes. However, pathological processes and mechanisms underlying neuropathic pain remain unclear. We aimed to identify overall profiles screen for genes potentially involved using transcriptome analysis of dorsal root ganglion mice treated streptozotocin (STZ). Using RNA sequencing, we identified differentially expressed (DEGs) between streptozotocin-treated controls, focusing on altered GABAergic neuron-related inflammatory pathways. Behavioral molecular analyses revealed a marked reduction neuronal markers (GAD65, GAD67, VGAT) increased pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) group compared controls. Intrathecal administration lentiviral vectors expressing transcription factors Ascl1 Lhx6 reversed hypersensitivity restored normal expression mediators. Protein-protein interaction (PPI) network five key proteins influenced by treatment, including those JunD/FosB/C-fos signaling pathway. These findings suggest that mitigate modulating function, responses, pain-related channels (TRPV1, Nav1.7). results provide basis developing factor-based therapies targeting neurons relief.