Lasting Epigenetic Influence of Early-life Adversity on the BDNF Gene

Overview

Journal Biol Psychiatry

Publisher Elsevier

Specialty Psychiatry

Date 2009 Jan 20

PMID 19150054

Citations 501

Authors

Tania L Roth

Farah D Lubin

Adam J Funk

J David Sweatt

Affiliations

Soon will be listed here.

Abstract

Background: Childhood maltreatment and early trauma leave lasting imprints on neural mechanisms of cognition and emotion. With a rat model of infant maltreatment by a caregiver, we investigated whether early-life adversity leaves lasting epigenetic marks at the brain-derived neurotrophic factor (BDNF) gene in the central nervous system.

Methods: During the first postnatal week, we exposed infant rats to stressed caretakers that predominately displayed abusive behaviors. We then assessed DNA methylation patterns and gene expression throughout the life span as well as DNA methylation patterns in the next generation of infants.

Results: Early maltreatment produced persisting changes in methylation of BDNF DNA that caused altered BDNF gene expression in the adult prefrontal cortex. Furthermore, we observed altered BDNF DNA methylation in offspring of females that had previously experienced the maltreatment regimen.

Conclusions: These results highlight an epigenetic molecular mechanism potentially underlying lifelong and transgenerational perpetuation of changes in gene expression and behavior incited by early abuse and neglect.

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References

De Bellis M . The psychobiology of neglect. Child Maltreat. 2005; 10(2):150-72. DOI: 10.1177/1077559505275116. View

Pfaffl M . A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res. 2001; 29(9):e45. PMC: 55695. DOI: 10.1093/nar/29.9.e45. View

Miller C, Sweatt J . Covalent modification of DNA regulates memory formation. Neuron. 2007; 53(6):857-69. DOI: 10.1016/j.neuron.2007.02.022. View

Fischer A, Sananbenesi F, Wang X, Dobbin M, Tsai L . Recovery of learning and memory is associated with chromatin remodelling. Nature. 2007; 447(7141):178-82. DOI: 10.1038/nature05772. View

Branchi I, Francia N, Alleva E . Epigenetic control of neurobehavioural plasticity: the role of neurotrophins. Behav Pharmacol. 2004; 15(5-6):353-62. DOI: 10.1097/00008877-200409000-00006. View

Oberlander T, Weinberg J, Papsdorf M, Grunau R, Misri S, Devlin A . Prenatal exposure to maternal depression, neonatal methylation of human glucocorticoid receptor gene (NR3C1) and infant cortisol stress responses. Epigenetics. 2008; 3(2):97-106. DOI: 10.4161/epi.3.2.6034. View

Darnaudery M, Maccari S . Epigenetic programming of the stress response in male and female rats by prenatal restraint stress. Brain Res Rev. 2008; 57(2):571-85. DOI: 10.1016/j.brainresrev.2007.11.004. View

Fleming A, Kraemer G, Gonzalez A, Lovic V, Rees S, Melo A . Mothering begets mothering: the transmission of behavior and its neurobiology across generations. Pharmacol Biochem Behav. 2002; 73(1):61-75. DOI: 10.1016/s0091-3057(02)00793-1. View

Miranda T, Jones P . DNA methylation: the nuts and bolts of repression. J Cell Physiol. 2007; 213(2):384-90. DOI: 10.1002/jcp.21224. View

10.

Barreto G, Schafer A, Marhold J, Stach D, Swaminathan S, Handa V . Gadd45a promotes epigenetic gene activation by repair-mediated DNA demethylation. Nature. 2007; 445(7128):671-5. DOI: 10.1038/nature05515. View

11.

Sanchez M . The impact of early adverse care on HPA axis development: nonhuman primate models. Horm Behav. 2006; 50(4):623-31. DOI: 10.1016/j.yhbeh.2006.06.012. View

12.

Numan M . Motivational systems and the neural circuitry of maternal behavior in the rat. Dev Psychobiol. 2006; 49(1):12-21. DOI: 10.1002/dev.20198. View

13.

Chahrour M, Jung S, Shaw C, Zhou X, Wong S, Qin J . MeCP2, a key contributor to neurological disease, activates and represses transcription. Science. 2008; 320(5880):1224-9. PMC: 2443785. DOI: 10.1126/science.1153252. View

14.

Siegmund K, Connor C, Campan M, Long T, Weisenberger D, Biniszkiewicz D . DNA methylation in the human cerebral cortex is dynamically regulated throughout the life span and involves differentiated neurons. PLoS One. 2007; 2(9):e895. PMC: 1964879. DOI: 10.1371/journal.pone.0000895. View

15.

Richards E . Inherited epigenetic variation--revisiting soft inheritance. Nat Rev Genet. 2006; 7(5):395-401. DOI: 10.1038/nrg1834. View

16.

Fenoglio K, Brunson K, Baram T . Hippocampal neuroplasticity induced by early-life stress: functional and molecular aspects. Front Neuroendocrinol. 2006; 27(2):180-92. PMC: 2937188. DOI: 10.1016/j.yfrne.2006.02.001. View

17.

Mill J, Tang T, Kaminsky Z, Khare T, Yazdanpanah S, Bouchard L . Epigenomic profiling reveals DNA-methylation changes associated with major psychosis. Am J Hum Genet. 2008; 82(3):696-711. PMC: 2427301. DOI: 10.1016/j.ajhg.2008.01.008. View

18.

Kress C, Thomassin H, Grange T . Active cytosine demethylation triggered by a nuclear receptor involves DNA strand breaks. Proc Natl Acad Sci U S A. 2006; 103(30):11112-7. PMC: 1544051. DOI: 10.1073/pnas.0601793103. View

19.

Febo M, Numan M, Ferris C . Functional magnetic resonance imaging shows oxytocin activates brain regions associated with mother-pup bonding during suckling. J Neurosci. 2005; 25(50):11637-44. PMC: 6726012. DOI: 10.1523/JNEUROSCI.3604-05.2005. View

20.

Sathanoori M, Dias B, Nair A, Banerjee S, Tole S, Vaidya V . Differential regulation of multiple brain-derived neurotrophic factor transcripts in the postnatal and adult rat hippocampus during development, and in response to kainate administration. Brain Res Mol Brain Res. 2004; 130(1-2):170-7. DOI: 10.1016/j.molbrainres.2004.08.002. View