PRENATAL METHAMPHETAMINE EXPOSURE COULD CAUSE CHRONIC ABNORMALITIES IN EPIGENOME ASSOCIATED WITH AUTISTIC LIKE BEHAVIOR, AN EXTENDED FOLLOW UP STUDY

Background and Aim : High rate of methamphetamine abuse among young adults and women of childbearing age makes it imperative to clarify the long-term effects of Methamphetamine exposure on the offspring. Present study aimed to assess the effects of parental Methamphetamine exposure in epigenetic programming and gene expression of children along with brain functions.Methods : All subjects were recruited before birth and sampling were conducted from day of birth in each six month until children get two years old. Hundred and fifty children with methamphetamine dependent mothers (with methamphetamine abuse during pregnancy) and 150 unrelated children with normal non psychiatric mothers were selected. Blood sampling and DNA and RNA extraction was operated. Genome-wide DNA methylation profiling of peripheral blood leukocytes conducted by using the Illumina Methylation 450K BeadChip platform. Genome expression profiling was conducted by using Affymetrix GeneChip Human Genome U133 plus 2.0 Array Platform. Gene expression data was confirmed by Real time PCR. Also electroencephalography performed for two years old children with 64 channel Biosemi EEG system.Results : Results showed seven CpG loci identified that their DNA methylation was significantly different in children with Meth-dependent mothers versus children with normal mothers. Pathway analysis revealed that hypermethylated CpG loci associated with Meth-dependent mothers were related to transcriptional regulation (P = 0.0004), mitogen-activated protein kinase (Mapk) signaling pathway (P = 0.002), synaptogenesis (P = 0.0004) and lymphocytes T maturation (P = 0.0006). Gene expression profiling showed mRNA level alteration in children with Meth-dependent mothers in 78 genes. Most of these genes were involved in synaptogenesis, neural plasticity, bioenergetic and immune system.Significant stronger activation in higher frequencies detected in frontal, parietal, and occipital regions of meth exposed children vs. normals. Conclusion : It seems that Methamphetamine abuse before and during the pregnancy period may affect epigenetic and expression profile of children and these changes could be remain years after birth. Both affected genes and neuroimaging changes are strongly similar to pattern of autistic children.findings may shed lights on molecular and neuronal effects of prenatal methamphetamine exposure as well as other pediatric developmental disorders.

کلیدواژه ها:

Methamphetamine ، prenatal ، electroencephalography ، epigenome