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Granulocyte Colony-Stimulating Factor Alleviates Bacterial-Induced Neuronal Apoptotic Damage in the Neonatal Rat Brain through Epigenetic Histone Modification. | LitMetric

Bacterial meningitis during the perinatal period may cause long-term neurological deficits. The study investigated whether bacterial lipopolysaccharide (LPS) derived from led to neuronal apoptosis with an impaired performance of long-term cognitive function involving the activation of histone modification in the TNF- gene promoter. Further, we looked into the therapeutic efficacy of granulocyte colony-stimulating factor (G-CSF) in a neonatal brain suffering from perinatal bacterial meningitis. We applied the following research techniques: neurobehavioral tasks, confocal laser microscopy, chromatin immunoprecipitation, and Western blotting. At postnatal day 10, the animals were subjected to LPS and/or G-CSF. The target brain tissues were then collected at P17. Some animals (P45) were studied using neurobehavioral tasks. The LPS-injected group revealed significantly increased expression of NF-B phosphorylation and trimethylated H3K4 in the gene promoter locus. Furthermore, the caspase-3, neuronal apoptosis expression, and an impaired performance in cognitive functions were also found in our study. Such deleterious outcomes described above were markedly alleviated by G-CSF therapy. This study suggests that selective therapeutic action sites of G-CSF through epigenetic regulation in the gene promoter locus may exert a potentially beneficial role for the neonatal brain suffering from perinatal bacterial-induced meningitis.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5816840PMC
http://dx.doi.org/10.1155/2018/9797146DOI Listing

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