Abstract
Insulin-like growth factor-1 (IGF-1) is a neurotrophic factor produced locally in the central nervous system which can promote axonal regeneration, protect motoneurons, and inhibit neuroinflammation. In this study, we used the zebrafish spinal transection model to investigate whether IGF-1 plays an important role in the recovery of motor function. Unlike mammals, zebrafish can regenerate axons and restore mobility in remarkably short period after spinal cord transection. Quantitative real-time PCR and immunofluorescence showed decreased IGF-1 expression in the lesion site. Double immunostaining for IGF-1 and Islet-1 (motoneuron marker)/GFAP (astrocyte marker)/Iba-1 (microglia marker) showed that IGF-1 was mainly expressed in motoneurons and was surrounded by astrocyte and microglia. Following administration of IGF-1 morpholino at the lesion site of spinal-transected zebrafish, swimming test showed retarded recovery of mobility, the number of motoneurons was reduced, and increased immunofluorescence density of microglia was caused. Our data suggested that IGF-1 enhances motoneuron survival and inhibits neuroinflammation after spinal cord transection in zebrafish, which suggested that IGF-1 might be involved in the motor recovery.
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Abbreviations
- CNS:
-
Central nervous system
- IGF-1:
-
Insulin-like growth factor-1
- MO:
-
Morpholino
- SPL MO:
-
Splice-blocking MO
- qRT-PCR:
-
Quantitative real-time PCR
- PBS:
-
Phosphate-buffered saline
- hpi:
-
Hours post injury
- dpi:
-
Days post injury
- wpi:
-
Weeks post injury
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Acknowledgements
This study was supported by Grants from The National Natural Science Foundation of China (81771384, 81801276), Postgraduate Research and Practice Innovation Program of Jiangsu Province (KYCX19_1893), Public Health Research Center at Jiangnan University (JUPH201801), and National First-Class Discipline Program of Food Science and Technology (JUFSTR20180101), Chinese Postdoctoral Science Foundation (2018M630512), and Wuxi Municipal Health Commission (1286010241190480).
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The experiment design: LZ, CC, YS, SH, CQ, LY; Spinal transection surgery: LZ, BZ, SH; Quantitative real-time PCR analysis: LZ, BZ, XJ, MS; Immunofluorescence and image analysis: LZ, BZ, SH, ZZ; Morpholino treatment: LZ, BZ, SH, ZZ, MS, LY; Behavioral test: LZ, BZ, YS; Statistical analysis: LZ, FW, ZZ, XJ, CQ, YS; Interpretation and editing of manuscript: LZ, CC, YS.
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This research was approved by the Animal Ethics Committee of Jiangnan University. The zebrafish work was performed according to Regulations for the Administration of Affairs Concerning Experimental Animals (approved by the State Council on October 31, 1998 and promulgated by Decree No. 2 of the State Science and Technology Commission on November 14, 1988).
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Zhao, L., Zhang, B., Huang, S. et al. Insulin-Like Growth Factor-1 Enhances Motoneuron Survival and Inhibits Neuroinflammation After Spinal Cord Transection in Zebrafish. Cell Mol Neurobiol 42, 1373–1384 (2022). https://doi.org/10.1007/s10571-020-01022-x
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DOI: https://doi.org/10.1007/s10571-020-01022-x