Epigenetic studies in insects and the valproic acid perspective

Abstract

Valproic acid in association with sodium valproate (VPA) is an important anticonvulsant drug used for decades to treat neurological disorders. VPA also acts as an epigenetic modulator by inhibiting histone deacetylases, permitting histone acetylation, affecting the DNA and histone methylation status and gene expression, and inducing chromatin remodeling. Insects represent an important animal model for studies in several areas of science. Their high phenotypic plasticity makes them alternative models for epigenetic studies. This brief review emphasizes recent reports on insect epigenetics and the contribution of studies on the VPA action in insects, including effects on epigenetic markers, extending the pharmacological understanding of the potential of this drug, and demonstrating the usefulness of insects as an alternative animal model to drug studies.

Nuclear Morphofunctional Organization and Epigenetic Characteristics in Somatic Cells of <em>Triatoma infestans</em> (Klug)

“…In the presence of VPA, T. infestans cells revealed unexpected results [52,78,79]. Onehour following the abdominal injection of a 0.05 mM VPA solution in T. infestans nymphs or after a 4-h in vitro culture of the Malpighian tubules of this insect in the presence of 0.05-0.5 mM VPA, unpacking of the chromocenter was demonstrated in a portion of the Malpighian tubule cells (Figure 4g) [52,79].…”

Ethnic Aspects of Valproic Acid P-Oxidation

“…The molecular mechanisms responsible for ethnic differences in VPA metabolism are explained by advances in molecular biology and population genetic studies in recent years [61,62]. In particular, significant differences in the population frequency of some variative ("mutant" or minor) SNVs in different countries of the world have been shown, which cause differences in the prevalence of patients with neurological diseases and mental disorders who are homozygous and heterozygous for the minor allele(s) of the gene(s) of the CYP family and associated with the impaired P-oxidation of VPA in the liver and the development of ADRs [63][64][65][66][67][68] (Table 2).…”

Nuclear Morphofunctional Organization and Epigenetic Characteristics in Somatic Cells of T. infestans (Klug, 1834)

“…Insects have been suggested as an alternative model for research on epigenetic effects promoted by VPA, because of their shorter generation intervals, the opportunity for analyzing larger samples, and diminished ethical concerns compared with those for the experimental use of mammals. Therefore, T. infestans may be considered an attractive candidate for evaluating pathway mechanisms underlying VPA action [ 78 ].…”

“…In the presence of VPA, T. infestans cells revealed unexpected results [ 52 , 78 , 79 ]. One-hour following the abdominal injection of a 0.05 mM VPA solution in T. infestans nymphs or after a 4-h in vitro culture of the Malpighian tubules of this insect in the presence of 0.05–0.5 mM VPA, unpacking of the chromocenter was demonstrated in a portion of the Malpighian tubule cells ( Figure 4 g) [ 52 , 79 ].…”