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Epigenetics: Stress and disease
Accepted Manuscript Title: Epigenetics: stress and disease Author: J. Regino Perez-Polo PII: DOI: Reference:
S0736-5748(17)30246-0 http://dx.doi.org/10.1016/j.ijdevneu.2017.08.002 DN 2212
To appear in:
Int. J. Devl Neuroscience
Please cite this article as: Perez-Polo, and disease.International Journal of http://dx.doi.org/10.1016/j.ijdevneu.2017.08.002
J.Regino, Epigenetics: stress Developmental Neuroscience
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Epigenetics: stress and disease
J. Regino Perez-Polo
In this issue we include two samples of work linking one component of epigenetic changes to prenatal stress in an animal model relevant to schizophrenia and another component of epigenetic changes to autistic behavioral dysfunction in humans. The paper by Blaze et al. (2017) focuses on changes in epigenetic regulation of BDNF expression by prenatal stress resulting in increased DNA methylation of cytosine in the prefrontal cortex of rats, an area known to play an important role in behavioral responses associated with schizophrenia and depression (Martinovich et al. 2007). Blaze et al (2017) also report on the shortening of telomeres in what are likely to be neurons of the medial prefrontal cortex in the prenatally stressed rats. These findings complement and support work showing similar findings in adult animals (Asok et al., 2014; Blaze et al., 2013; Roth et al., 2009; Roth et al., 2014). The authors also report on selective sexual outcomes for DNA methylation as opposed to telomere shortening; in that prenatal stress has a sex independent effect on telomere shortening. This could be due to the fragility of the Y chromosome and increased susceptibility to DNA methylation compared to X chromosomes (Hill and Fitch,2012; Uddin et al., 2013).
The second paper by Zhubi et al. (2017) focuses on epigenetic repressor mechanisms that are associated with promoter function and DNA methylation, both aspects of chromatin molecular remodeling. Working with human frontal cortex autopsy samples from Autism Spectrum Disorder patients, they show significant changes in the repressor proteins Reeling and glutamate decarboxylase 67 but not DNA methylation. Here the more significant changes were not in DNA methylation but in levels of the Reeling and gluatamate decarboxlalse 67 in autism spectrum disorder brain cortex patient samples in contrast to Blaze et al.
The demonstrated tissue specificity, sex selective responses and mechanistic epigenetic differences described in these two papers, an animal model of prenatal stress and human samples from diagnosed autistic patients is representative of the complex role of epigenetics in phenotype regulation (Grayson and Guidotti, 2016) and in the case of the animal model is consistent with other reports of transgenerational non-genetic changes; of which some have been shown to also be sex specific (Blaze and Roth, 2015; Infante et al., 2013).
While representing a small sample of the epigenetic literature, these two papers reflect the complex linkage between environmental influences in development process to linkages to brain specific areas and sex specific changes already shown to have transgenerational effects (Infante et al., 2013). Although a distinctions between developmental epigenetic processes and transgenerational epigenetic can be made on the basis of failure in the resetting of chromatin states in reproduction, it is likely to be an integrated process with sporadic evolutionary consequences (see also Blaze and Roth, 2015).
While an understanding of the broader significance of sex specific consequences of environmental effects on epigenetic regulation across generations on evolutionary impact on health is not at hand, these two papers proved further support for the imperative to pursue the study of the relationships between transient environmental stressors and neuropathology with sporadic multigenerational consequences.
References
Asok, A., Bernard, K., Rosen, J.B., Dozier, M., Roth, T.L., 2014. Infant-caregiver experiences alter telomere length in the brain. PLoS One 9, e101437.
Blaze, J., Scheuing, L., Roth, T.L., 2013. Differential methylation of genes in the medial prefrontal cortex of developing and adult rats following exposure to maltreatment or nurturing care during infancy. Developmental Neuroscience 35, 306-316.
Blaze, J., Asok, A., Roth, T.L., 2015. The long-term impact of adverse caregiving environments on epigenetic modifications and telomeres. Frontiers in Behavioral Neuroscience 9, 79.
Grayson DR, Guidotti A., 2016. Merging data from genetic and epigenetic approaches to better understand autistic spectrum disorder. Epigenomics. 2016; 8(1):85-104. doi: 10.2217/epi.15.92.
Hill CA, Fitch RH. 2012. Sex differences in mechanisms and outcome of neonatal hypoxiaischemia in rodent models: implications for sex-specific neuroprotection in clinical neonatal practice. Neurology Research International. doi: 10.1155/2012/867531
Infante SK. Rea HC. Perez-Polo JR. (2013). Transgenerational effects of neonatal hypoxiaischemia in progeny. Internat.J. Dev. Neurosci. 31:398-405.
Martinowich, K., Manji, H., Lu, B., 2007. New insights into BDNF function in depression and anxiety. Nature Neuroscience 10, 1089-1093.
Prokopuk L; Western PS; Stringer JM. 2015. Transgenerational epigenetic inheritance: adaptation through the germline epigenome?. Epigenomics. 7(5):829-46, 2015.
Roth, T.L., Lubin, F.D., Funk, A.J., Sweatt, J.D., 2009. Lasting epigenetic influence of early-life
adversity on the BDNF gene. Biological Psychiatry 65, 760-769.
Roth, T.L., Matt, S., Chen, K., Blaze, J., 2014. Bdnf DNA methylation modifications in the hippocampus and amygdala of male and female rats exposed to different caregiving environments outside the homecage. Developmental Psychobiology 56, 1755-1763.
Uddin M; Sipahi L; Li J; Koenen KC. 2013. Sex differences in DNA methylation may contribute to risk of PTSD and depression: a review of existing evidence. Depression & Anxiety. 30(12):1151-60.
Zhou Q. G., Hu Y., Wu D. L., Zhu L. J., Chen C., Jin X., et al. . (2011). Hippocampal telomerase is involved in the modulation of depressive behaviors. J. Neurosci. 31, 12258–12269. 10.1523/jneurosci.0805-11.2011
S0736-5748(17)30246-0 http://dx.doi.org/10.1016/j.ijdevneu.2017.08.002 DN 2212
To appear in:
Int. J. Devl Neuroscience
Please cite this article as: Perez-Polo, and disease.International Journal of http://dx.doi.org/10.1016/j.ijdevneu.2017.08.002
J.Regino, Epigenetics: stress Developmental Neuroscience
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Epigenetics: stress and disease
J. Regino Perez-Polo
In this issue we include two samples of work linking one component of epigenetic changes to prenatal stress in an animal model relevant to schizophrenia and another component of epigenetic changes to autistic behavioral dysfunction in humans. The paper by Blaze et al. (2017) focuses on changes in epigenetic regulation of BDNF expression by prenatal stress resulting in increased DNA methylation of cytosine in the prefrontal cortex of rats, an area known to play an important role in behavioral responses associated with schizophrenia and depression (Martinovich et al. 2007). Blaze et al (2017) also report on the shortening of telomeres in what are likely to be neurons of the medial prefrontal cortex in the prenatally stressed rats. These findings complement and support work showing similar findings in adult animals (Asok et al., 2014; Blaze et al., 2013; Roth et al., 2009; Roth et al., 2014). The authors also report on selective sexual outcomes for DNA methylation as opposed to telomere shortening; in that prenatal stress has a sex independent effect on telomere shortening. This could be due to the fragility of the Y chromosome and increased susceptibility to DNA methylation compared to X chromosomes (Hill and Fitch,2012; Uddin et al., 2013).
The second paper by Zhubi et al. (2017) focuses on epigenetic repressor mechanisms that are associated with promoter function and DNA methylation, both aspects of chromatin molecular remodeling. Working with human frontal cortex autopsy samples from Autism Spectrum Disorder patients, they show significant changes in the repressor proteins Reeling and glutamate decarboxylase 67 but not DNA methylation. Here the more significant changes were not in DNA methylation but in levels of the Reeling and gluatamate decarboxlalse 67 in autism spectrum disorder brain cortex patient samples in contrast to Blaze et al.
The demonstrated tissue specificity, sex selective responses and mechanistic epigenetic differences described in these two papers, an animal model of prenatal stress and human samples from diagnosed autistic patients is representative of the complex role of epigenetics in phenotype regulation (Grayson and Guidotti, 2016) and in the case of the animal model is consistent with other reports of transgenerational non-genetic changes; of which some have been shown to also be sex specific (Blaze and Roth, 2015; Infante et al., 2013).
While representing a small sample of the epigenetic literature, these two papers reflect the complex linkage between environmental influences in development process to linkages to brain specific areas and sex specific changes already shown to have transgenerational effects (Infante et al., 2013). Although a distinctions between developmental epigenetic processes and transgenerational epigenetic can be made on the basis of failure in the resetting of chromatin states in reproduction, it is likely to be an integrated process with sporadic evolutionary consequences (see also Blaze and Roth, 2015).
While an understanding of the broader significance of sex specific consequences of environmental effects on epigenetic regulation across generations on evolutionary impact on health is not at hand, these two papers proved further support for the imperative to pursue the study of the relationships between transient environmental stressors and neuropathology with sporadic multigenerational consequences.
References
Asok, A., Bernard, K., Rosen, J.B., Dozier, M., Roth, T.L., 2014. Infant-caregiver experiences alter telomere length in the brain. PLoS One 9, e101437.
Blaze, J., Scheuing, L., Roth, T.L., 2013. Differential methylation of genes in the medial prefrontal cortex of developing and adult rats following exposure to maltreatment or nurturing care during infancy. Developmental Neuroscience 35, 306-316.
Blaze, J., Asok, A., Roth, T.L., 2015. The long-term impact of adverse caregiving environments on epigenetic modifications and telomeres. Frontiers in Behavioral Neuroscience 9, 79.
Grayson DR, Guidotti A., 2016. Merging data from genetic and epigenetic approaches to better understand autistic spectrum disorder. Epigenomics. 2016; 8(1):85-104. doi: 10.2217/epi.15.92.
Hill CA, Fitch RH. 2012. Sex differences in mechanisms and outcome of neonatal hypoxiaischemia in rodent models: implications for sex-specific neuroprotection in clinical neonatal practice. Neurology Research International. doi: 10.1155/2012/867531
Infante SK. Rea HC. Perez-Polo JR. (2013). Transgenerational effects of neonatal hypoxiaischemia in progeny. Internat.J. Dev. Neurosci. 31:398-405.
Martinowich, K., Manji, H., Lu, B., 2007. New insights into BDNF function in depression and anxiety. Nature Neuroscience 10, 1089-1093.
Prokopuk L; Western PS; Stringer JM. 2015. Transgenerational epigenetic inheritance: adaptation through the germline epigenome?. Epigenomics. 7(5):829-46, 2015.
Roth, T.L., Lubin, F.D., Funk, A.J., Sweatt, J.D., 2009. Lasting epigenetic influence of early-life
adversity on the BDNF gene. Biological Psychiatry 65, 760-769.
Roth, T.L., Matt, S., Chen, K., Blaze, J., 2014. Bdnf DNA methylation modifications in the hippocampus and amygdala of male and female rats exposed to different caregiving environments outside the homecage. Developmental Psychobiology 56, 1755-1763.
Uddin M; Sipahi L; Li J; Koenen KC. 2013. Sex differences in DNA methylation may contribute to risk of PTSD and depression: a review of existing evidence. Depression & Anxiety. 30(12):1151-60.
Zhou Q. G., Hu Y., Wu D. L., Zhu L. J., Chen C., Jin X., et al. . (2011). Hippocampal telomerase is involved in the modulation of depressive behaviors. J. Neurosci. 31, 12258–12269. 10.1523/jneurosci.0805-11.2011