Changes in the methylation profile of DNA extracted from brain tissues of rats after exposure to trace elements by using of capillary electrophoresis

RATTI, S; GRELA D; GAGLIO, E.; ALVAREZ, EO; VIZIOLI, NM

Charlottesville

Simposio; 29th International Symposium MicroScale Bioseparations; 2013

The HSR (Hand Skill Relative, OMIM 139900) gene is associated to handedness, brain asymmetry, reading-writing abilities and susceptibility to schizophrenia. This gene has been described to be subjected to epigenetic regulation, and one of the main molecular mechanisms whereby this regulation is performed is by methylation of DNA. In a previous study, primary school children from a certain area of La Rioja, province of Argentina, characterized by the abundance of mineral deposits, were found to have altered phenotypic expression attributed to the HSR. A hypothesis was raised considering the epigenetic regulation of the HSR gene and its susceptibility to environmental influences; trace elements present in this region could be exogenous factors involved in the altered expression attributed to this gene. The objective of the present work was to test in a cognitive lateralization and associate behavioral responses rat model, the possible biological effect of ZnTe as a representative trace element on some spontaneous and natural behavioral responses similar to HSR expression of humans, and to determine the methylation profile of DNA extracted from brain tissues of those rats. ZnTe treatment was applied in drinking water to pregnant mother animals along all gestation, delivery, weaning and preadolescent periods. Results showed that ZnTe treatment produced two different effects. Treated young rats displayed excitatory motor and selective motivated exploration responses in a behavioral automatic activity device. Furthermore, the same animals showed impairments in motivated and lateralized behavioral displayed in a lateralized exploratory labyrinth. In addition, natural defensive responses were attenuated in ZnTe treated rats in a different test measuring defensive behavior. The determination of the methylation pattern of DNA in brain prefrontal cortex and hippocampus was performed by capillary electrophoresis. Experimental conditions were carefully optimized in order to avoid interferences from sample matrix during the analysis. It was found that the ratio of non-methylated- to methylated cytosine increased in ZnTe treated animals, suggesting an epigenetic change on the same line that was observed in children in the previous study of this laboratory. In conclusion, the rat model used in the present study confirms some of the previous evidence found in humans. References 1. Ratti SG, Vizioli NM, Álvarez EO. Am. J. Neuroprotec. Neuroregen. 2010, 2 (1), 65-70.