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. 2019 Apr 30;60(2):71-77.
doi: 10.3325/cmj.2019.60.71.

Brain derived neurotrophic factor expression and DNA methylation in response to subchronic valproic acid and/or aldosterone treatment

Katarina Buzgoova, Jan Graban, Lucia Balagova, Natasa Hlavacova, Daniela Jezova  1
Affiliations

Brain derived neurotrophic factor expression and DNA methylation in response to subchronic valproic acid and/or aldosterone treatment

Katarina Buzgoova et al. Croat Med J. .

Abstract

Aim: To test the hypothesis that valproic acid treatment positively affects brain-derived neurotrophic factor (BDNF) expression and DNA methylation in the hippocampus and brain cortex of rats simultaneously treated with aldosterone.

Methods: Male Sprague-Dawley rats (N=40) were treated for two weeks with valproic acid (100 mg/1 kg body weight/d) in drinking water and aldosterone (2 μg/100 g body weight/d) or placebo via subcutaneous osmotic minipumps.

Results: Treatment with valproic acid did not modify BDNF gene expression in the hippocampus but reduced BDNF mRNA levels in the brain cortex. Valproic acid treatment marginally enhanced global DNA methylation in the frontal cortex. BDNF expression negatively correlated with DNA methylation in the hippocampus of valproic acid-treated rats. An unexpected finding was that aldosterone treatment significantly decreased global DNA methylation in the hippocampus.

Conclusion: The effect of valproic acid on BDNF expression in the brain may depend on the extent of pathological changes present at the time of treatment onset. The observed negative correlation between BDNF expression and DNA methylation in the hippocampus of valproic acid-treated rats encourages further studies.

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Figures

Figure 1
Figure 1
Effects of valproic acid (VPA) and aldosterone treatments on the brain-derived neurotrophic factor (BDNF) expression in the brain cortex and hippocampus. Each value represents the mean ± standard deviation (n = 10 rats/group). Statistical significance as tested by two-way ANOVA with the main factors of VPA treatment and aldosterone treatment. Presented results represent a relative value, namely a ratio between the quantity of measured gene and geometric mean of the quantities of reference genes (21).
Figure 2
Figure 2
Effects of valproic acid (VPA) and aldosterone treatments on the global DNA methylation in the brain cortex and hippocampus. Each value represents the mean ± standard deviation (n = 10 rats/group). Statistical significance as tested by two-way ANOVA with main factors of valproic treatment and aldosterone treatment. 5-mC % – percentage of methylated DNA (5-methylcytosine).
Figure 3
Figure 3
The negative correlation between the expression of brain-derived neurotrophic factor (BDNF) and global methylation in the hippocampus in the whole sample (r = - 0.41, P = 0.014). 5-mC % – percentage of methylated DNA (5-methylcytosine).
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References

    1. Dussaule C, Bouilleret V. Psychiatric effects of antiepileptic drugs in adults. Geriatr Psychol Neuropsychiatr Vieil. 2018;16:181–8. - PubMed
    1. Liu D, Qiu HM, Fei HZ, Hu XY, Xia HJ, Wang LJ, et al. Histone acetylation and expression of mono-aminergic transmitters synthetases involved in CUS-induced depressive rats. Exp Biol Med (Maywood) 2014;239:330–6. doi: 10.1177/1535370213513987. - DOI - PubMed
    1. Ximenes JC, Neves KR, Leal LK, do Carmo MR, Brito GA, Naffah-Mazzacoratti M, et al. Valproic acid neuroprotection in the 6-OHDA model of Parkinson’s disease is possibly related to its anti-inflammatory and HDAC inhibitory properties. J Neurodegener Dis. 2015;2015:313702. - PMC - PubMed
    1. Monti B, Polazzi E, Contestabile A. Biochemical, molecular and epigenetic mechanisms of valproic acid neuroprotection. Curr Mol Pharmacol. 2009;2:95–109. doi: 10.2174/1874467210902010095. - DOI - PubMed
    1. Silva MR, Correia AO, Dos Santos GCA, Parente LLT, de Siqueira KP, Lima DGS, et al. Neuroprotective effects of valproic acid on brain ischemia are related to its HDAC and GSK3 inhibitions. Pharmacol Biochem Behav. 2018;167:17–28. doi: 10.1016/j.pbb.2018.02.001. - DOI - PubMed