論文 - 詳細
| RRC ID | 87642 |
|---|---|
| 著者 | Saied-Santiago K, Baxter M, Mathiaparanam J, Granato M. |
| タイトル | Serotonin neuromodulation directs optic nerve regeneration. |
| ジャーナル | Development |
| Abstract |
Optic nerve (ON) regeneration in mammalian systems is limited by an overshadowing dominance of inhibitory factors. This has severely hampered the identification of pro-regenerative pathways. Here, we take advantage of the regenerative capacity of larval zebrafish to identify pathways that promote ON regeneration. From a small molecule screen, we identified modulators of serotonin (5-HT) signaling that inhibit ON regeneration. We find that several serotonin type-1 (5-HT1) receptor genes are expressed in retinal ganglion cells during regeneration and that inhibiting 5-HT1 receptors or components of the 5-HT pathway selectively impedes ON regeneration. We show that 5-HT1 receptor signaling is dispensable during ON development yet is required for regenerating axons to emerge from the injury site. Blocking 5-HT receptors once ON axons have crossed the chiasm does not inhibit regeneration, suggesting a selective role for 5-HT receptor signaling early during ON regeneration. Finally, we show that agonist-mediated activation of 5-HT1 receptors leads to enhanced and ectopic axonal regrowth. Combined, our results provide evidence for mechanisms through which serotonin-dependent neuromodulation directs ON regeneration in vivo. |
| 巻・号 | 152(13) |
| 公開日 | 2025-7-1 |
| DOI | 10.1242/dev.204334 |
| PII | 368298 |
| PMID | 40521655 |
| PMC | PMC12276806 |
| MeSH | Animals Axons / metabolism Axons / physiology Nerve Regeneration* / drug effects Nerve Regeneration* / physiology Optic Nerve* / drug effects Optic Nerve* / physiology Optic Nerve Injuries Receptors, Serotonin, 5-HT1 / genetics Receptors, Serotonin, 5-HT1 / metabolism Retinal Ganglion Cells / metabolism Serotonin* / metabolism Signal Transduction / drug effects Zebrafish / physiology Zebrafish Proteins / genetics Zebrafish Proteins / metabolism |
| IF | 5.611 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ゼブラフィッシュ | Tol-056 |