Sodium butyrate prevents radiation-induced cognitive impairment by restoring pCREB/BDNF expression

Sodium butyrate is a histone deacetylase inhibitor that affects various types of brain damages.To investigate the effects of sodium butyrate on hippocampal dysfunction that occurs after whole-brain irradiation in animal models and the effect of sodium butyrate on radiation exposure-induced cognitive impairments,adult C57BL/6 mice were intraperitoneally treated with 0.6 g/kg sodium butyrate before exposure to 10 Gy cranial irradiation.Cognitive impairment in adult C57BL/6 mice was evaluated via an object recognition test 30 days after irradiation.We also detected the expression levels of neurogenic cell markers(doublecortin)and phosphorylated cAMP response element binding protein/brain-derived neurotrophic factor.Radiation-exposed mice had decreased cognitive function and hippocampal doublecortin and phosphorylated cAMP response element binding protein/brain-derived neurotrophic factor expression.Sodium butyrate pretreatment reversed these changes.These findings suggest that sodium butyrate can improve radiation-induced cognitive dysfunction through inhibiting the decrease in hippocampal phosphorylated cAMP response element binding protein/brain-derived neurotrophic factor expression.The study procedures were approved by the Institutional Animal Care and Use Committee of Korea Institute of Radiological Medical Sciences(approval No.KIRAMS16-0002)on December 30,2016.

Epigenetic mechanisms involved in the neuroprotective effect of scorpion extract in a Parkinson's disease murine model based on multi-omics approach

OBJECTIVE: To investigate whether scorpion extract elicits a neuroprotective effect in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-treated mice models, and the genes associated with the therapeutic effects using RNA sequencing(seq)analysis.METHODS: This study investigated the changes in interaction between messenger ribonucleic acid(m RNA) expression and deoxyribonucleic acid(DNA) methylation related to the protective effects of scorpion extracts, in the substantia nigra(SN)region of a MPTP-induced Parkinson's disease(PD)model.RESULTS: In this model, scorpion extracts attenuated the motor impairment as demonstrated by the rotarod and open field tests. Scorpion extracts consistently attenuated the decrease of tyrosine hydroxylase(TH) positive neural cells in the SN and striatum of mice. We profiled genomewide DNA methylation using Methyl-Seq and measured the transcriptome using RNA-Seq in murine SN in the following groups: vehicle-treated MPTP-induced PD mice and scorpion extracttreated MPTP-induced PD mice. In total, 13 479 differentially expressed genes were identified in association with the anti-PD effect of the scorpion extract, mainly in the promoter and coding regions.Among them, 47 were negatively correlated downregulated genes. Nineteen genes out of 47 downregulated genes were negatively correlated with the expression of the other 28 genes. Among these genes, SGSM1 was related to dopaminergic neurons including dopamine transporters, TH, dihydroxyphenylalanine decarboxylase, and dopamine D2 receptor.CONCLUSION: This study provides insights into the anti-parkinsonian effects of scorpion extract and reveals the epigenetic targets in its therapeutic mechanism.