Behavioral epigenetics
Behavioral epigenetics is the field of study examining the role of epigenetics in shaping animal (including human) behaviour.[1] Epigenetic gene regulation involves changes other than to the sequence of DNA and includes changes to histones (proteins around which DNA is wrapped) and DNA methylation.[2] These epigenetic changes can influence the growth of neurons in the developing brain[3] as well as modify activity of the neurons in the adult brain.[4][5] Together, these epigenetic changes on neuron structure and function can have a marked influence on an organism's behavior.[1]
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[edit] Discovery
The first documented example of epigenetics affecting behavior was provided by Meaney and Szyf. While working at McGill University in Montréal in 2004, they discovered that the type of mothering a rat receives in infancy determines how that rat responds to stress later in life. Rat pups that receive a less nurturing upbringing are more sensitive to stress throughout their life-span. This stress sensitivity is linked to a down-regulation in the expression of the glucocorticoid receptor in the brain. In turn, this down-regulation was found to be a consequence of the extent of methylation in the promoter region of the glucocorticoid receptor gene.[1][6] This pioneering work in rodents has been hard to replicate in humans because of a general lack of human brain tissue for measurement of epigenetic changes.[1] The first study that has directly linked epigenetic changes in human brain tissue to behavior involved post-mortem brains of people who committed suicide, half of whom had been abused as children. Those who had been abused had a lower expression of glucocorticoid receptor due to increased methylation in the promoter region of the glucocorticoid receptor gene. These observations in humans closely parallel the earlier rat studies.[1][7]
[edit] Mechanisms
[edit] Histone modification
Histone modification has a strong effect on transcriptional regulation. Furthermore synaptic plasticity and long-term memory are dependent on transcription.[8] One factor that has been shown to critical to synaptic plasticity and the formation of long-term memory is the transcriptional coactivator CREB-binding protein which has histone acetyltransferase (HAT) activity.[8]
[edit] DNA methylation
Changes in DNA methylation of the promoter regions of reelin and Bdnf genes affects hippocampal long-term potentiation that in turn contextual fear conditioning.[8]
[edit] References
- ^ a b c d e Miller G (July 2010). "Epigenetics. The seductive allure of behavioral epigenetics". Science 329 (5987): 24–7. doi:10.1126/science.329.5987.24. PMID 20595592.
- ^ Pennisi E (August 2001). "Behind the scenes of gene expression". Science 293 (5532): 1064–7. doi:10.1126/science.293.5532.1064. PMID 11498570.
- ^ Juliandi B, Abematsu M, Nakashima K (August 2010). "Epigenetic regulation in neural stem cell differentiation". Dev. Growth Differ. 52 (6): 493–504. doi:10.1111/j.1440-169X.2010.01175.x. PMID 20608952.
- ^ Ma DK, Marchetto MC, Guo JU, Ming GL, Gage FH, Song H (November 2010). "Epigenetic choreographers of neurogenesis in the adult mammalian brain". Nat. Neurosci. 13 (11): 1338–44. doi:10.1038/nn.2672. PMID 20975758.
- ^ Sun J, Sun J, Ming GL, Song H (March 2011). "Epigenetic regulation of neurogenesis in the adult mammalian brain". Eur. J. Neurosci. 33 (6): 1087–93. doi:10.1111/j.1460-9568.2011.07607.x. PMC 3076719. PMID 21395852. //www.ncbi.nlm.nih.gov/pmc/articles/PMC3076719/.
- ^ Weaver IC, Cervoni N, Champagne FA, D'Alessio AC, Sharma S, Seckl JR, Dymov S, Szyf M, Meaney MJ (August 2004). "Epigenetic programming by maternal behavior". Nat. Neurosci. 7 (8): 847–54. doi:10.1038/nn1276. PMID 15220929.
- ^ McGowan PO, Sasaki A, D'Alessio AC, Dymov S, Labonté B, Szyf M, Turecki G, Meaney MJ (March 2009). "Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse". Nat. Neurosci. 12 (3): 342–8. doi:10.1038/nn.2270. PMC 2944040. PMID 19234457. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2944040/.
- ^ a b c Malvaez M, Barrett RM, Wood MA, Sanchis-Segura C (2009). "Epigenetic mechanisms underlying extinction of memory and drug-seeking behavior". Mamm. Genome 20 (9-10): 612–23. doi:10.1007/s00335-009-9224-3. PMC 3157916. PMID 19789849. //www.ncbi.nlm.nih.gov/pmc/articles/PMC3157916/.
