El Chemali, Lea and Boutary, Suzan and Liu, Song and Liu, Guo-Jun and Middleton, Ryan J. and Banati, Richard B. and Bahrenberg, Gregor and Rupprecht, Rainer and Schumacher, Michael and Massaad-Massade, Liliane (2024) GRT-X Stimulates Dorsal Root Ganglia Axonal Growth in Culture via TSPO and Kv7.2/3 Potassium Channel Activation. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 25 (13): 7327. ISSN 1661-6596, 1422-0067
Full text not available from this repository.Abstract
GRT-X, which targets both the mitochondrial translocator protein (TSPO) and the Kv7.2/3 (KCNQ2/3) potassium channels, has been shown to efficiently promote recovery from cervical spine injury. In the present work, we investigate the role of GRT-X and its two targets in the axonal growth of dorsal root ganglion (DRG) neurons. Neurite outgrowth was quantified in DRG explant cultures prepared from wild-type C57BL6/J and TSPO-KO mice. TSPO was pharmacologically targeted with the agonist XBD173 and the Kv7 channels with the activator ICA-27243 and the inhibitor XE991. GRT-X efficiently stimulated DRG axonal growth at 4 and 8 days after its single administration. XBD173 also promoted axonal elongation, but only after 8 days and its repeated administration. In contrast, both ICA27243 and XE991 tended to decrease axonal elongation. In dissociated DRG neuron/Schwann cell co-cultures, GRT-X upregulated the expression of genes associated with axonal growth and myelination. In the TSPO-KO DRG cultures, the stimulatory effect of GRT-X on axonal growth was completely lost. However, GRT-X and XBD173 activated neuronal and Schwann cell gene expression after TSPO knockout, indicating the presence of additional targets warranting further investigation. These findings uncover a key role of the dual mode of action of GRT-X in the axonal elongation of DRG neurons.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PERIPHERAL-NERVE REGENERATION; TRANSLOCATOR PROTEIN; MESSENGER-RNA; SCHWANN-CELLS; EXPRESSION; NEURONS; DIFFERENTIATION; MOUSE; MODEL; TSPO; peripheral benzodiazepine receptor; potassium channels; Kv7.2/3; KCNQ2/3; GRT-X; axonal growth; gene expression; dorsal root ganglia |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Psychiatrie und Psychotherapie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 28 Jan 2026 08:30 |
| Last Modified: | 28 Jan 2026 08:30 |
| URI: | https://pred.uni-regensburg.de/id/eprint/65154 |
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