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

الملخص EN

Bacterial meningitis during the perinatal period may cause long-term neurological deficits.

The study investigated whether bacterial lipopolysaccharide (LPS) derived from E.

coli.

led to neuronal apoptosis with an impaired performance of long-term cognitive function involving the activation of histone modification in the TNF-α 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-κB phosphorylation and trimethylated H3K4 in the TNFA 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 TNFA gene promoter locus may exert a potentially beneficial role for the neonatal brain suffering from perinatal bacterial-induced meningitis.