Introduction: Learning and memory are two of the fundamental cognitive functions that confer us the ability to accumulate knowledge from our experiences. Although we use these two mental skills continuously, understanding the molecular basis of learning and memory is very challenging. Methylation modification of DNA is an epigenetic mechanism which is the most important process of neurons. DNA methylation regulates neural activities and memory formation via the control of gene expression in neurons, and relate these studies to various age-related neurological disorders that affect cognitive functions.And many types of human neurological disorders, including mental retardation (like MR) syndromes and neurodegenerative diseases, display cognitive defects as reflected by impaired learning and memory abilities , many other diseases with complex profiles, the underlying causes of most neural diseases are often heterogeneous and involve the interplays among different genes and environmental factors.
Methods: The function and behavior of neurons, like any other types of cells, are ultimately determined by the genes expressed in them. Synaptic connectivity among neurons serves as the physical basis for memory formation, which often entails gene products (mRNA or protein) from a vast number of neural activity-related genes. The molecular basis of synapse-dependent LTM formation can thus be understood by studying the regulatory mechanisms of gene expression in the neural network. DNA methylation and histone modifications regulate gene expression via reversible and dynamic chromatin remodeling processes. DNA methylation and histone acetylation can regulate gene expression synergistically through protein mediators such as the methyl-CpG binding protein MeCP2.also DNA methylation modification of the genome occurs primarily on cytosines located in CpG dinucleotides, posttranslational modifications of histone proteins are much more complex and affect multiple residues at over 30 sites within the N-terminal tails of histones. Histone methylation alone can appear in the form of mono-, di-, and tri-methylation. Even more complex, these different forms of methylation can occur on different amino acid residues that are located at different positions.
Results: Folate is an important substrate in one-carbon metabolism . Folate provides the dietary source of methyl group for biological methylation. It is required for the conversion of homocysteine to methionine and the formation of S-adenosylmethionine . S-adenosylmethionine participates in biological methylation reactions, which generates S-adenosylhomocysteine that subsequently forms homocysteine. Folate-depletion can cause genomic DNA hypomethylation, which can be reversed upon dietary folate restoration. Folate depletion can also lead to cellular accumulation of S-adenosylmethionine and dramatically increase blood homocysteine levels. S-adenosylmethionine is a potent inhibitor of Dnmt activity through the product inhibition pathway and can lead to genome hypomethylation. The disruption of homocysteine metabolism can adversely affect both the developing and the adult brain. The disruption of one-carbon metabolism can repress the proliferation of cultured multipotent neuroepithelial progenitor cells and alter cell cycle distribution. And also folic acid deficiency dramatically reduces the number of proliferating cells in the dentate gyrus of the hippocampus in adults.Since neurogenesis in the adult hippocampus is possibly pivotal in learning and memory and in recovery from injury, these results suggest that dietary folate deficiency can affect neurogenesis via inhibiting the proliferation of neuronal progenitor cells in the adult brain
Conclusion: DNA methylation controls learning and memory