An epigenetic mechanism refers to any heritable influence (in the progeny of cells or individuals) on chromosome or gene function that is not accompanied by a change in DNA sequence (Yoder et al 1997); a change in phenotype without a change in genotype. These changes may last through generations of cell divisions. Although it was once thought that there was no new generation of neurons in the nervous system, studies have shown that the brain retains neural stem cells (NSCs) into adulthood, and neurogenesis continues to occur. Neural stem cells (NSCs) are the initial cells found in the nervous system and differentiate into the main cell types: oligodendrocytes, astrocytes and neurons. There are three epigenetic mechanisms which are involved in each of these differentiations; these are DNA methylation, histone modifications and noncoding ribonucleic acid (ncRNA) expression, which lead to activating and silencing the correct genes at each step. Epigenetic mechanisms have been implicated play a huge role in several functions in the nervous system such as in neurogenesis, neuronal- glial differentiation and also have roles in higher functions such as memory and cognition. A major mechanism in epigenetics is DNA methylation. DNA methylation occurs in two mechanisms and is the addition of a methyl (-CH₃) group through a covalent bond to a cytosine side chain. DNA methylation is catalysed by a group of enzymes called DNA methyltransferases (DNMTs). DNMT adds methyl groups to cytosine residues. Cytosines have to be immediately followed by a Guanine In order to be methylated, these are called CpG dinucleotides. Around 70% of these dinucleotides get methylated whilst the rest are in clusters called CpG islands. There are two typ...
... middle of paper ...
...Glass, Non-coding RNAs as regulators of gene expression and epigenetics, 2011, oxford journals, 90 (3), p430-440
J. David Sweatt. (2009). Experience-dependent Epigenetic Modifications in the CNS. Biol Psychiatry. 65 (3), 191-197.
Chwang WB, O'Riordan KJ, Levenson JM, Sweatt JD. ERK/MAPK regulates hippocampal histone phosphorylation following contextual fear conditioning. Learn Mem. 2006;13:322–328
Kaili Anier, Anti Kalda, epigenetics in the nervous system. Learn Mem. 2006; 43-72
Atd Bio, Epigenetics, 2013,
Feng. J. Chang, H. Li E., Fan G. Dynamic expression of de novo DNA Methyltransferases DNMT3a and DNMT3b in the central nervou system. J Neruoscience Res, 2006 (79), p734-746
Korzus E, Rosenfeld MG, Mayford M. CBP histone acetyltransferase activity is a critical component of memory consolidation. Neuron 2004;42:961-72
Min, K. J., Hyun, K. D., Lee, Y., Jin, P. S., & Hoon, R. J. (2014). Distinct roles of the hippocampus
McEwen, B. S., & Gianaros, P. J. (2011). Stress-and allostasis-induced brain plasticity. Annual review of medicine, 62, 431-445.
---. “Epigenetics Modifications and Viral Infections.” Frontiers in Genetics. Frontiers Media S.A, 2007-2014. Web. 31 Mar. 2014. .
The function of the hippocampus is crucial for LTM consolidation and with recollection and familiarity, however recent research in mice and recent development in optogenetics has enhanced a new understanding between hippocampus and fear memory recall.
DNA methylation is catalyzed by the enzyme: DNA methyl trasnferase (DNMTs). Methylation of DNA segments leads to the silencing of transposable elements. Hence this mechanism is repressive to transcription, by that enhancing genomic stability. However, there exist “CpG” islands that are associated with gene promoters that escape methylation hence stability.
One of the most commonly described mechanisms is altered DNA methylation, which has been noted in paternal folate deficiency7, maternal under-nourishment during pregnancy6,7, paternal high fat diets2, and paternal low protein diets3. Another mechanism is established by microRNA’s ability to regulate DNA methylation. Certain microRNA’s are known to downregulate DNA methyltransferase enzymes that function to maintain global methylation status in the genome.6 It has been proposed that environmental exposures, like nutrition, can change sperm microRNAs leading to modifications in DNA methylation.11 Histone modifications in spermatids, such as acetylation, occur in another commonly described mechanism. These diet related changes affects the structure of chromatin, which can lead to increased risk damage to DNA and thus poor sperm outcomes.6 Further influences that lead to epigenetic changes during spermatogenesis include the following: increased testicular temperature, hyperleptinemia, hyperinsulinemia, and genotoxic metabolites due to paternal fat accumulation causing increased oxidative injury to sperm cell DNA.6 These epigenetic changes are thought to influence and accelerate genetic variation that is thought to drive the evolution of a
As the human body goes through different experiences, the brain grows, develops, and changes according to the environmental situations it has been exposed to. Some of these factors include drugs, stress, hormones, diets, and sensory stimuli. [1] Neuroplasticity can be defined as the ability of the nervous system to respond to natural and abnormal stimuli experienced by the human body. The nervous system then reorganizes the brain’s structure and changes some of its function to theoretically repair itself by forming new neurons. [2] Neuroplasticity can occur during and in response to many different situations that occur throughout life. Some examples of these situations are learning, diseases, and going through therapy after an injury.
Pitman, R. K., Milad, M. R., Igoe, S. A., Vangel, M. G., Orr, S. P., Tsareva, A., & ... Nader, K. (2011). Systemic mifepristone blocks reconsolidation of cue-conditioned fear; Propranolol prevents this effect. Behavioral Neuroscience, 125(4), 632-638. doi:10.1037/a0024364
McGowan, Patrick O., et al. "Broad Epigenetic Signature Of Maternal Care In The Brain Of Adult Rats." Plos ONE 6.2 (2011): 1-11. Academic Search Complete. Web. 3 Apr. 2014.
The MTHFR enzyme is required for methylation. In the article, Methylation Problems Lead to 100s of Diseases, it is stated that “Methylation is the process of taking a single carbon and three hydrogens, known as a methyl group, and
Neurogenesis is the creation of new brain cells. Even though neural connections are “wired early and are resistant to change” we now know through neurogenesis and neuroplasticity, that these connections can and do change over our lifespan (Fishbane, 2007, p. 397). The most rapid period of neurogenesis occurs at the embryonic state of human development (Rutecki, 1992), called embryogenesis. At this stage, progenitor cells, and neural stem cells, which are similar to progenitor cells, differentiate into specific types of cells, and in the case of the human brain, these cells are called neurons (Zhang & Jiao, 2015). A human baby can produce billions of neurons and millions of neural connections, or “neural pathways,” by the age of 3, more than any period in a typical human’s lifetime. In fact, at this stage in human development, the average child is producing around 700 neural connections per second (InBrief: The Science of Early Childhood Development, 2012). “Experience alters the brain, even as we age…whenever we learn something new, attitudes, perspectives, or behaviors, we are changing the physical structure of the brain” (Fishbane, 2007, p.
A recent field of biology, called epigenetics, is rapidly transforming previous ideas on the impact of genes. The...
Hyman, S. E. & Nestler, E. J. The Molecular Foundations of Psychiatry. Washington Amer. Psych., 1993. (cited as 7 & 8)
...e in the neurodevelopment cycle, such as increased neuronal dysfunction with decreased connectivity and increases in loss of neuropril and extrinsic factor like substance abuse, developmental stress, relationship problem(Elder, Evans and Nizette, 2007).