Exploring Potential Mechanisms by which Early Life Stress Impairs Adult Hippocampal Neurogenesis

Authors

  • Ananya Bhatt Brookfield Central High School
  • Nicole Katchur Mentor, Princeton University

DOI:

https://doi.org/10.47611/jsrhs.v11i1.2435

Keywords:

Early life stress, Adult hippocampal neurogenesis, Telomeres, Telomerase, DNA Methylation

Abstract

Prolonged stressful experiences prior to adolescence have been linked to an increased risk of a multitude of neurological disorders, from depression and anxiety to schizophrenia and bipolar disorder. In particular, early life stress (ELS) has been shown to significantly impair adult hippocampal neurogenesis (AHN). While the long-term effects of early life stress are well studied, the underlying mechanisms through which ELS impairs AHN are still largely unknown. This paper reviews the current literature surrounding early life stress and AHN and discusses potential mediators that impact AHN during ELS including changes in telomere length, alterations in telomerase activity, and dysregulation of DNA methylation.

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Heim, C., Shugart, M., Craighead, W., & Nemeroff, C. (2010). Neurobiological and psychiatric consequences of child abuse and neglect. Developmental Psychobiology, 52(7), 671-690. doi: 10.1002/dev.20494.

(2021). Retrieved 29 November 2021, from https://www.biorxiv.org/content/10.1101/417832v1.full.pdf

Li M, D'Arcy C, Meng X (2016): Maltreatment in childhood substantially increases the risk of adult depression and anxiety in prospective cohort studies: systematic review, meta-analysis, and proportional attributable fractions. Psychol Med. 46:717- 730.

Establishing a Link Between Attention Deficit Disorder/Attention Deficit Hyperactivity Disorder and Childhood Physical Abuse. (2021). Journal Of Aggression, Maltreatment & Trauma. Retrieved from https://www.tandfonline.com/doi/abs/10.1080/10926771.2014.873510

Sapolsky, R., Krey, L., & McEwen, B. (1984). Glucocorticoid-sensitive hippocampal neurons are involved in terminating the adrenocortical stress response. Proceedings Of The National Academy Of Sciences, 81(19), 6174-6177. doi: 10.1073/pnas.81.19.6174

Jankord, R., & Herman, J. (2008). Limbic Regulation of Hypothalamo-Pituitary-Adrenocortical Function during Acute and Chronic Stress. Annals Of The New York Academy Of Sciences, 1148(1), 64-73. doi: 10.1196/annals.1410.012

(2021). Retrieved 22 August 2021, from https://www.jneurosci.org/content/jneuro/22/3/635.full.pdf

Calem, M., Bromis, K., McGuire, P., Morgan, C., & Kempton, M. (2017). Meta-analysis of associations between childhood adversity and hippocampus and amygdala volume in non-clinical and general population samples. Neuroimage: Clinical, 14, 471-479. doi: 10.1016/j.nicl.2017.02.016

Brydges, N., Moon, A., Rule, L., Watkin, H., Thomas, K., & Hall, J. (2018). Sex specific effects of pre-pubertal stress on hippocampal neurogenesis and behaviour. Translational Psychiatry, 8(1). doi: 10.1038/s41398-018-0322-4

Functions and Dysfunctions of Adult Hippocampal Neurogenesis. (2021). Retrieved 23 August 2021, from https://www.annualreviews.org/doi/abs/10.1146/annurev-neuro-071013-014134

Tyrka, A., Price, L., Kao, H., Porton, B., Marsella, S., & Carpenter, L. (2010). Childhood Maltreatment and Telomere Shortening: Preliminary Support for an Effect of Early Stress on Cellular Aging. Biological Psychiatry, 67(6), 531-534. doi: 10.1016/j.biopsych.2009.08.014

van Steensel B, Smogorzewska A & de Lange T (1998) TRF2 protects human telomeres from end-to-end fusions. Cell 92: 401–413 https://doi.org/10.1016/S0092-8674(00)80932-0

de Lange T (2005) Shelterin: the protein complex that shapes and safeguards human telomeres. Genes Dev. 19: 2100–2110 https://doi.org/10.1101/gad.1346005

Flores, I., & Blasco, M. (2010). The role of telomeres and telomerase in stem cell aging. FEBS Letters, 584(17), 3826-3830. doi: 10.1016/j.febslet.2010.07.042

Lu, C., Fu, W., & Mattson, M. (2001). Telomerase protects developing neurons against DNA damage-induced cell death. Developmental Brain Research, 131(1-2), 167-171. doi: 10.1016/s0165-3806(01)00237-1

Moore, L., Le, T., & Fan, G. (2012). DNA Methylation and Its Basic Function. Neuropsychopharmacology, 38(1), 23-38. doi: 10.1038/npp.2012.112

Shen L, Kondo Y, Guo Y, Zhang J, Zhang L, Ahmed S et al (2007). Genome-wide profiling of DNA methylation reveals a class of normally methylated CpG island promoters. PLoS Genet 3: 2023–2036.

Meissner A, Mikkelsen TS, Gu H, Wernig M, Hanna J, Sivachenko A et al (2008). Genome-scale DNA methylation maps of pluripotent and differentiated cells. Nature 454: 766–770.

Jobe, E., & Zhao, X. (2017). DNA Methylation and Adult Neurogenesis. Brain Plasticity, 3(1), 5-26. doi: 10.3233/bpl-160034

Tyrka, A., Price, L., Kao, H., Porton, B., Marsella, S., & Carpenter, L. (2010). Childhood Maltreatment and Telomere Shortening: Preliminary Support for an Effect of Early Stress on Cellular Aging. Biological Psychiatry, 67(6), 531-534. doi: 10.1016/j.biopsych.2009.08.014

Schneper, L., Brooks-Gunn, J., Notterman, D., & Suomi, S. (2016). Early-Life Experiences and Telomere Length in Adult Rhesus Monkeys: An Exploratory Study. Psychosomatic Medicine,78(9),1066-1071.doi: 10.1097/psy.0000000000000402

Understanding the stress response - Harvard Health. (2011). Retrieved 7 October 2021, from https://www.health.harvard.edu/staying-healthy/understanding-the-stress-response

Epel, E., Lin, J., Dhabhar, F., Wolkowitz, O., Puterman, E., Karan, L., & Blackburn, E. (2010). Dynamics of telomerase activity in response to acute psychological stress. Brain, Behavior, And Immunity, 24(4), 531-539. doi: 10.1016/j.bbi.2009.11.018

Lin, J., Epel, E., & Blackburn, E. (2012). Telomeres and lifestyle factors: Roles in cellular aging. Mutation Research/Fundamental And Molecular Mechanisms Of Mutagenesis, 730(1-2), 85-89. doi: 10.1016/j.mrfmmm.2011.08.003

Damjanovic, A., Yang, Y., Glaser, R., Kiecolt-Glaser, J., Nguyen, H., & Laskowski, B. et al. (2007). Accelerated Telomere Erosion Is Associated with a Declining Immune Function of Caregivers of Alzheimer’s Disease Patients. The Journal Of Immunology, 179(6), 4249-4254. doi: 10.4049/jimmunol.179.6.4249

Schutte, N., & Malouff, J. (2014). A meta-analytic review of the effects of mindfulness meditation on telomerase activity. Psychoneuroendocrinology,42,45-48. doi: 10.1016/j.psyneuen.2013.12.017

Epel, E., Blackburn, E., Lin, J., Dhabhar, F., Adler, N., Morrow, J., & Cawthon, R. (2004). Accelerated telomere shortening in response to life stress. Proceedings Of The National Academy Of Sciences,101(49),17312-17315. doi: 10.1073/pnas.0407162101

Daubenmier, J., Lin, J., Blackburn, E., Hecht, F., Kristeller, J., & Maninger, N. et al. (2012). Changes in stress, eating, and metabolic factors are related to changes in telomerase activity in a randomized mindfulness intervention pilot study. Psychoneuroendocrinology, 37(7), 917-928. doi: 10.1016/j.psyneuen.2011.10.008

Ostenfeld T, Caldwell MA, Prowse KR, Linskens MH, Jauniaux E, Svendsen CN (2000) Human neural precursor cells express low levels of telomerase in vitro and show diminishing cell proliferation with extensive axonal outgrowth following transplantation

Klapper W, Shin T, Mattson MP (2001) Differential regulation of telomerase activity and TERT expression during brain development in mice. J Neurosci Res 64:252–260

Fu, W., Lu, C., & Mattson, M. (2002). Telomerase Mediates the Cell Survival-Promoting Actions of Brain-Derived Neurotrophic Factor and Secreted Amyloid Precursor Protein in Developing Hippocampal Neurons. The Journal Of Neuroscience, 22(24), 10710-10719. doi: 10.1523/jneurosci.22-24-10710.2002

Fu W, Killen M, Pandita T, Mattson MP (2000) The catalytic subunit of telomerase is expressed in developing brain neurons and serves a cell survival-promoting function. J Mol Neurosci 14:3–15

Waterhouse, E. G. et al. BDNF promotes differentiation and maturation of adult-born neurons through GABAergic transmission. J Neurosci 32, 14318–14330 (2012).

Chan, J. P., Cordeira, J., Calderon, G. A., Iyer, L. K. & Rios, M. Depletion of central BDNF in mice impedes terminal differentiation of new granule neurons in the adult hippocampus. Mol Cell Neurosci 39, 372–383 (2008).

(2021). Retrieved 8 September 2021, from http://ir.nsfc.gov.cn/paperDownload/1000014388547.pdf

Beal, M. (1992). Mechanisms of excitotoxicity in neurologic diseases. The FASEB Journal, 6(15), 3338-3344. doi: 10.1096/fasebj.6.15.1464368

Fryer, H., Knox, R., Strittmatter, S., & Kalb, R. (1999). Excitotoxic Death of a Subset of Embryonic Rat Motor Neurons In Vitro. Journal Of Neurochemistry, 72(2), 500-513. doi: 10.1046/j.1471-4159.1999.0720500.x

Lyko, F. (2017). The DNA methyltransferase family: a versatile toolkit for epigenetic regulation. Nature Reviews Genetics, 19(2), 81-92. doi: 10.1038/nrg.2017.80

Feng J, Chang H, Li E, Fan G. 2005. Dynamic expression of de novo DNA methyltransferases Dnmt3a and Dnmt3b in the central nervous system. J Neurosci Res 79:734–746.

Wu, Z., Huang, K., Yu, J., Le, T., Namihira, M., & Liu, Y. et al. (2012). Dnmt3a regulates both proliferation and differentiation of mouse neural stem cells. Journal Of Neuroscience Research, 90(10), 1883-1891. doi: 10.1002/jnr.23077

Feng, J., Zhou, Y., Campbell, S., Le, T., Li, E., & Sweatt, J. et al. (2010). Dnmt1 and Dnmt3a maintain DNA methylation and regulate synaptic function in adult forebrain neurons. Nature Neuroscience, 13(4), 423-430. doi: 10.1038/nn.2514

Anier, K., Malinovskaja, K., Pruus, K., Aonurm-Helm, A., Zharkovsky, A., & Kalda, A. (2014). Maternal separation is associated with DNA methylation and behavioural changes in adult rats. European Neuropsychopharmacology, 24(3), 459-468. doi: 10.1016/j.euroneuro.2013.07.012

Urb, M., Anier, K., Matsalu, T., Aonurm-Helm, A., Tasa, G., & Koppel, I. et al. (2019). Glucocorticoid Receptor Stimulation Resulting from Early Life Stress Affects Expression of DNA Methyltransferases in Rat Prefrontal Cortex. Journal Of Molecular Neuroscience, 68(1), 99-110. doi: 10.1007/s12031-019-01286-z

Wu, X., & Zhang, Y. (2017). TET-mediated active DNA demethylation: mechanism, function and beyond. Nature Reviews Genetics, 18(9), 517-534. doi: 10.1038/nrg.2017.33

López-Moyado, I., Tsagaratou, A., Yuita, H., Seo, H., Delatte, B., & Heinz, S. et al. (2019). Paradoxical association of TET loss of function with genome-wide DNA hypomethylation. Proceedings Of The National Academy Of Sciences, 116(34), 16933-16942. doi: 10.1073/pnas.1903059116

Mohr, F., Döhner, K., Buske, C., & Rawat, V. (2011). TET Genes: new players in DNA demethylation and important determinants for stemness. Experimental Hematology, 39(3), 272-281. doi: 10.1016/j.exphem.2010.12.004

Zhang, R., Cui, Q., Murai, K., Lim, Y., Smith, Z., & Jin, S. et al. (2013). Tet1 Regulates Adult Hippocampal Neurogenesis and Cognition. Cell Stem Cell, 13(2), 237-245. doi: 10.1016/j.stem.2013.05.006

Wu, H., D’Alessio, A., Ito, S., Xia, K., Wang, Z., & Cui, K. et al. (2011). Dual functions of Tet1 in transcriptional regulation in mouse embryonic stem cells. Nature, 473(7347), 389-393. doi: 10.1038/nature09934

Rosenberg, T., Kisliouk, T., Cramer, T., Shinder, D., Druyan, S., & Meiri, N. (2020). Embryonic Heat Conditioning Induces TET-Dependent Cross-Tolerance to Hypothalamic Inflammation Later in Life. Frontiers In Genetics, 11. doi: 10.3389/fgene.2020.00767

Massart, R., Suderman, M., Provencal, N., Yi, C., Bennett, A., Suomi, S., & Szyf, M. (2014). Hydroxymethylation and DNA methylation profiles in the prefrontal cortex of the non-human primate rhesus macaque and the impact of maternal deprivation on hydroxymethylation. Neuroscience, 268, 139-148. doi: 10.1016/j.neuroscience.2014.03.021

Yao, B., Christian, K., He, C., Jin, P., Ming, G., & Song, H. (2016). Epigenetic mechanisms in neurogenesis. Nature Reviews Neuroscience, 17(9), 537-549. doi: 10.1038/nrn.2016.70

Fogelman, N., & Canli, T. (2019). Early Life Stress, Physiology, and Genetics: A Review. Frontiers In Psychology, 10. doi: 10.3389/fpsyg.2019.01668

Harlow, H., Dodsworth, R., & Harlow, M. (1965). Total social isolation in monkeys. Proceedings Of The National Academy Of Sciences, 54(1), 90-97. doi: 10.1073/pnas.54.1.90

Estrogen's Effects on the Female Body. (2021). Retrieved 8 October 2021, from https://www.hopkinsmedicine.org/health/conditions-and-diseases/estrogens-effects-on-the-female-body

Stirone, C., Duckles, S., Krause, D., & Procaccio, V. (2005). Estrogen Increases Mitochondrial Efficiency and Reduces Oxidative Stress in Cerebral Blood Vessels. Molecular Pharmacology, 68(4), 959-965. doi: 10.1124/mol.105.014662

Jobe, E., & Zhao, X. (2017). DNA Methylation and Adult Neurogenesis. Brain Plasticity, 3(1), 5-26. doi: 10.3233/bpl-160034

Stirone, C., Duckles, S., Krause, D., & Procaccio, V. (2005). Estrogen Increases Mitochondrial Efficiency and Reduces Oxidative Stress in Cerebral Blood Vessels. Molecular Pharmacology, 68(4), 959-965. doi: 10.1124/mol.105.014662

Feagin, Joe R., and Steve Rutter. Systemic Racism: A Theory of Oppression. Routledge, 2006

Racism and Health I: Pathways and Scientific Evidence - David R. Williams, Selina A. Mohammed, 2013. (2021). American Behavioral Scientist. Retrieved from https://journals.sagepub.com/doi/abs/10.1177/0002764213487340

Chang, S., Walker, S., Grantham-McGregor, S., & Powell, C. (2002). Early childhood stunting and later behavior and school achievement. Journal Of Child Psychology And Psychiatry, 43(6), 775-783. doi: 10.1111/1469-7610.00088

Gottlieb, T., & Oren, M. (1998). p53 and apoptosis. Seminars In Cancer Biology, 8(5), 359-368. doi: 10.1006/scbi.1998.0098

Published

02-28-2022

How to Cite

Bhatt, A., & Katchur, N. (2022). Exploring Potential Mechanisms by which Early Life Stress Impairs Adult Hippocampal Neurogenesis . Journal of Student Research, 11(1). https://doi.org/10.47611/jsrhs.v11i1.2435

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Section

HS Review Articles