Epigenetic and Autism


Autism or Autism Spectrum Disorder (ASD) is a lifelong disorder of brain development. This disorder is characterized by challenges in social interaction, restricted in repetitive behavior and activities related with nonverbal and verbal communication. There is no cure for autism and even the actual reason for autism is still not fully understood and till now in under research. Researchers have found that there are certain gene mutations those may influence the brain development in early stages. Epigenetics refers to the process of change in gene expression by altering or modifying DNA methylation or histone modification without a change in genetic code. Here phenotype change occurs which can be influenced by various disease state, age , environment or lifestyle.
Gene expression is affected when epigenetic signals are mediated to change chromatin. These signals are stable and the epigenetic abnormalities may play a role in the pathophysiology of autism. When an abnormal epigenetic signal causes abnormal gene expression it is called epimutation. These epimutations may arise from somatic cell when studied on neoplasms. The dysregulation of epigenetic in developing autism is caused by conventional mutations or mutations in proteins. Development and regulation of central nervous system is influenced by methyl CpG binding protein 2 (MeCp2). MeCp2 is thought to play a role in regulating epigenetic by silencing gene. It was found that abnormal methylation in synaptic contacts decreases the MeCp2 expression and results in autism. There are three possible mechanisms of epimutations by which syndromic autism may occur. It can be Fragile X syndrome, which is an X-linked disorder and mental retardation, dysmorphisms are its characteristics. Again there is Rett syndrome where terminal differentiation and maturation of neurons are hampered and cause abnormal cell signaling, metabolism and neuroprotection because of abnormal gene regulation. The third mechanism is the Angleman syndrome which is caused by abnormal methylation. Several studies have been performed that showed a link between methyl group metabolism and abnormalities of this disorder. The process of folate metabolism is critical for DNA methylation. Methyl group metabolic maintenance is performed by folate through its assistance in recycling of homocycteine to methionine. In offspring there is an increased risk for changing folate carrier gene which may lead to autism in offspring. Researches supported that the risk of autism can be reduced by taking folic acid with vitamins or by taking folic acid rich diet in periconceptional period. Medication, infection and environmental toxins if exposed in the prenatal period that may go through some epigenetic mechanism and cause autism. These mechanisms may include abnormal mutation in noncoding RNA or protein. Again, during pregnancy nutritional imbalance can results in various disease state because this state determines which disease related genes can be affected in such condition. Many studies showed that cytochrome P450 is associated with autism. If hydroxylation and activation of vitamin D by cytochrome P450 undergoes epigenetic mutation it may lead to cancer also. For neurodevelopment and neuronal growth vitamin D is very important but if there is a deficiency or defect in vitamin D metabolism then it may cause autism. Again these sites can be a potential therapeutic target if extensive study is done on them and epigenetic gene mutation in the central nervous system can be controlled.
Not only epigenetics causes autism but also it is associated with the pathology in the central nervous system that include psychiatric disorders e.g. schizophrenia, addiction and even depression. There are certain challenges to study epigenetics for example, technical or statistical limitations. Biological limitation includes disease complexity and access to tissue. But if those are overcome then it can offer promising strategies for better therapeutic targets.

Sabera Rahman is an undergrad student of Department of Pharmacy, East West University. She has interest on pharmacology and pharmaceutical chemistry. She can be reached at sabera.rahman@ymail.com

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