Repeated Stress Exposure in Mid-adolescence Attenuates Behavioral, Noradrenergic, and Epigenetic Effects of Trauma-like Stress in Early Adult Male Rats

Overview

Journal Sci Rep

Specialty Science

Date 2020 Oct 22

PMID 33087769

Citations 11

Authors

Lauren E Chaby

Nareen Sadik

Nicole A Burson

Scott Lloyd

Kelly ODonnel

Jesse Winters

Alana C Conti

Israel Liberzon

Shane A Perrine

Affiliations

Soon will be listed here.

Abstract

Stress in adolescence can regulate vulnerability to traumatic stress in adulthood through region-specific epigenetic activity and catecholamine levels. We hypothesized that stress in adolescence would increase adult trauma vulnerability by impairing extinction-retention, a deficit in PTSD, by (1) altering class IIa histone deacetylases (HDACs), which integrate effects of stress on gene expression, and (2) enhancing norepinephrine in brain regions regulating cognitive effects of trauma. We investigated the effects of adolescent-stress on adult vulnerability to severe stress using the single-prolonged stress (SPS) model in male rats. Rats were exposed to either (1) adolescent-stress (33-35 postnatal days) then SPS (58-60 postnatal days; n = 14), or (2) no adolescent-stress and SPS (58-60 postnatal days; n = 14), or (3) unstressed conditions (n = 8). We then measured extinction-retention, norepinephrine, HDAC4, and HDAC5. As expected, SPS exposure induced an extinction-retention deficit. Adolescent-stress prior to SPS eliminated this deficit, suggesting adolescent-stress conferred resiliency to adult severe stress. Adolescent-stress also conferred region-specific resilience to norepinephrine changes. HDAC4 and HDAC5 were down-regulated following SPS, and these changes were also modulated by adolescent-stress. Regulation of HDAC levels was consistent with the pattern of cognitive effects of SPS; only animals exposed to SPS without adolescent-stress exhibited reduced HDAC4 and HDAC5 in the prelimbic cortex, hippocampus, and striatum. Thus, HDAC regulation caused by severe stress in adulthood interacts with stress history such that seemingly conflicting reports describing effects of adolescent stress on adult PTSD vulnerability may stem in part from dynamic HDAC changes following trauma that are shaped by adolescent stress history.

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References

McGowan P, Sasaki A, DAlessio A, Dymov S, Labonte B, Szyf M . Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse. Nat Neurosci. 2009; 12(3):342-8. PMC: 2944040. DOI: 10.1038/nn.2270. View

Renthal W, Maze I, Krishnan V, Covington 3rd H, Xiao G, Kumar A . Histone deacetylase 5 epigenetically controls behavioral adaptations to chronic emotional stimuli. Neuron. 2007; 56(3):517-29. DOI: 10.1016/j.neuron.2007.09.032. View

Mather M, Clewett D, Sakaki M, Harley C . Norepinephrine ignites local hotspots of neuronal excitation: How arousal amplifies selectivity in perception and memory. Behav Brain Sci. 2015; 39:e200. PMC: 5830137. DOI: 10.1017/S0140525X15000667. View

Ramamoorthi K, Fropf R, Belfort G, Fitzmaurice H, McKinney R, Neve R . Npas4 regulates a transcriptional program in CA3 required for contextual memory formation. Science. 2011; 334(6063):1669-75. PMC: 4038289. DOI: 10.1126/science.1208049. View

Geracioti Jr T, Baker D, Ekhator N, West S, Hill K, Bruce A . CSF norepinephrine concentrations in posttraumatic stress disorder. Am J Psychiatry. 2001; 158(8):1227-30. DOI: 10.1176/appi.ajp.158.8.1227. View

Levine A, Worrell T, Zimnisky R, Schmauss C . Early life stress triggers sustained changes in histone deacetylase expression and histone H4 modifications that alter responsiveness to adolescent antidepressant treatment. Neurobiol Dis. 2011; 45(1):488-98. PMC: 3225638. DOI: 10.1016/j.nbd.2011.09.005. View

Beach S, Brody G, Todorov A, Gunter T, Philibert R . Methylation at 5HTT mediates the impact of child sex abuse on women's antisocial behavior: an examination of the Iowa adoptee sample. Psychosom Med. 2010; 73(1):83-7. PMC: 3016449. DOI: 10.1097/PSY.0b013e3181fdd074. View

Khan S, Liberzon I . Topiramate attenuates exaggerated acoustic startle in an animal model of PTSD. Psychopharmacology (Berl). 2003; 172(2):225-9. DOI: 10.1007/s00213-003-1634-4. View

Cedar H, Bergman Y . Linking DNA methylation and histone modification: patterns and paradigms. Nat Rev Genet. 2009; 10(5):295-304. DOI: 10.1038/nrg2540. View

10.

Perroud N, Paoloni-Giacobino A, Prada P, Olie E, Salzmann A, Nicastro R . Increased methylation of glucocorticoid receptor gene (NR3C1) in adults with a history of childhood maltreatment: a link with the severity and type of trauma. Transl Psychiatry. 2012; 1:e59. PMC: 3309499. DOI: 10.1038/tp.2011.60. View

11.

He M, Zhang B, Wei X, Wang Z, Fan B, Du P . HDAC4/5-HMGB1 signalling mediated by NADPH oxidase activity contributes to cerebral ischaemia/reperfusion injury. J Cell Mol Med. 2013; 17(4):531-42. PMC: 3822653. DOI: 10.1111/jcmm.12040. View

12.

Ferland C, Schrader L . Regulation of histone acetylation in the hippocampus of chronically stressed rats: a potential role of sirtuins. Neuroscience. 2010; 174:104-14. PMC: 3020273. DOI: 10.1016/j.neuroscience.2010.10.077. View

13.

Markham J, Mullins S, Koenig J . Periadolescent maturation of the prefrontal cortex is sex-specific and is disrupted by prenatal stress. J Comp Neurol. 2012; 521(8):1828-43. PMC: 4479145. DOI: 10.1002/cne.23262. View

14.

Ciechanover A . The ubiquitin-proteasome proteolytic pathway. Cell. 1994; 79(1):13-21. DOI: 10.1016/0092-8674(94)90396-4. View

15.

Chen C, Chaby L, Nazeer S, Liberzon I . Effects of Trauma in Adulthood and Adolescence on Fear Extinction and Extinction Retention: Advancing Animal Models of Posttraumatic Stress Disorder. Front Behav Neurosci. 2018; 12:247. PMC: 6220349. DOI: 10.3389/fnbeh.2018.00247. View

16.

Chaby L, Cavigelli S, Hirrlinger A, Caruso M, Braithwaite V . Chronic unpredictable stress during adolescence causes long-term anxiety. Behav Brain Res. 2014; 278:492-5. DOI: 10.1016/j.bbr.2014.09.003. View

17.

Green J, McLaughlin K, Berglund P, Gruber M, Sampson N, Zaslavsky A . Childhood adversities and adult psychiatric disorders in the national comorbidity survey replication I: associations with first onset of DSM-IV disorders. Arch Gen Psychiatry. 2010; 67(2):113-23. PMC: 2822662. DOI: 10.1001/archgenpsychiatry.2009.186. View

18.

DE SOUZA E, Van Loon G . Brain serotonin and catecholamine responses to repeated stress in rats. Brain Res. 1986; 367(1-2):77-86. DOI: 10.1016/0006-8993(86)91581-7. View

19.

Spear L . Adolescent neurodevelopment. J Adolesc Health. 2013; 52(2 Suppl 2):S7-13. PMC: 3982854. DOI: 10.1016/j.jadohealth.2012.05.006. View

20.

George S, Rodriguez-Santiago M, Riley J, Rodriguez E, Liberzon I . The effect of chronic phenytoin administration on single prolonged stress induced extinction retention deficits and glucocorticoid upregulation in the rat medial prefrontal cortex. Psychopharmacology (Berl). 2014; 232(1):47-56. DOI: 10.1007/s00213-014-3635-x. View