Aspartate-glutamate carrier 1 regulates myelination in preterm rats with periventricular leukomalacia

doi:10.12307/2023.485

Abstract

Abstract: BACKGROUND: Periventricular leukomalacia is one of the most serious medical complications in preterm infants and there is yet no effective treatment for periventricular leukomalacia.
OBJECTIVE: To investigate the effects of aspartate-glutamate carrier 1 (AGC1) on myelination in preterm rats with periventricular leukomalacia.
METHODS: Sixty male Sprague-Dawley rat pups on postnatal day 2 were randomly divided into sham group (n=30) and periventricular leukomalacia group (n=30). For in vitro studies, periventricular white matter tissues were isolated from five rat pups on postnatal day 2 to prepare white matter progenitor cells and establish an experimental oxygen-glucose deprivation model. Before the establishment of periventricular leukomalacia and oxygen-glucose deprivation models, pcDNA3-AGC1 plasmids were used to treat rats or cells. RT-qPCR was used to detect the expression of AGC1 in periventricular white matter tissue and cells at different time points after modeling. The expression of myelin basic protein and allophycocyanin was detected by immunofluorescence, and the ultrastructure of the corona radiate and corpus callosum was observed by electron microscopy at 14 days after periventricular leukomalacia.
RESULTS AND CONCLUSION: (1) Compared with the sham group, the expression of myelin basic protein and the number of allophycocyanin-positive oligodendrocytes and myelinated axons were significantly decreased in the periventricular leukomalacia group at 14 days after periventricular leukomalacia (P < 0.01). (2) AGC1 mRNA expression began to significantly increase in the white matter tissue at 12-24 hours (P < 0.05) and decreased significantly at 72 hours-14 days (P < 0.05) after periventricular leukomalacia in vivo, compared with 0 hour. (3) Under control conditions in vitro, AGC1 mRNA expression was increased significantly at 24-48 hours after oxygen-glucose deprivation (P < 0.05), and the AGC1 mRNA expression and the formation of myelin basic protein+/AGC1+ oligodendrocytes decreased significantly at 7-14 days after oxygen-glucose deprivation (P < 0.05), compared to 0 hour in the control group. (4) The myelin basic protein staining of the myelin sheath and the number of allophycocyanin-positive oligodendrocytes and myelinated axons in the pcDNA3-AGC1 treated group were significantly higher than those in the pcDNA3-NC group at 14 days after periventricular leukomalacia (P < 0.05). (5) In vitro, enhanced AGC1 expression further promoted the differentiation of oligodendrocyte precursor cells into myelin basic protein+/AGC1+ oligodendrocytes at 72 hours, 7 days, and 14 days after oxygen-glucose deprivation (P < 0.05). In conclusion, the expression of AGC1 is down-regulated in the preterm rat model of periventricular leukomalacia and the cell model of oxygen-glucose deprivation in vitro. Up-regulation of AGC1 can promote oligodendrocyte differentiation and myelination.

Key words: aspartate-glutamate carrier 1, periventricular leukomalacia, premature birth, oligodendrocyte, myelin sheath

CLC Number:

Wang Lizhen, Yang Caijin, Chen Rong, Li Ling. Aspartate-glutamate carrier 1 regulates myelination in preterm rats with periventricular leukomalacia[J]. Chinese Journal of Tissue Engineering Research, 2023, 27(33): 5263-5269.

Figures/Tables 5

References

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