Intermittent Ethanol During Adolescence Leads to Lasting Behavioral Changes in Adulthood and Alters Gene Expression and Histone Methylation in the PFC

Overview

Journal Front Mol Neurosci

Specialty Molecular Biology

Date 2017 Oct 12

PMID 29018328

Citations 37

Authors

Jennifer T Wolstenholme

Tariq Mahmood

Guy M Harris

Shahroze Abbas

Michael F Miles

Affiliations

Soon will be listed here.

Abstract

Adolescents primarily consume alcohol in binges, which can be particularly harmful to the developing frontal cortex and increase risk for an adult alcohol use disorder. We conducted a study investigating immediate and long lasting changes to the prefrontal cortex (PFC) transcriptome to determine the molecular mechanisms underlying adult ethanol behavioral sensitivity following binge ethanol in adolescence. DBA/2J mice were orally dosed with 4 g/kg ethanol intermittently from day 29 to 42. Adolescent mice were tested for anxiety-like behavior and ethanol sensitivity using the loss of righting reflex task. As adults, mice were tested for cognitive changes using the novel object recognition task, ethanol-induced anxiolysis and ethanol sensitivity. Adolescent binge ethanol altered ethanol sensitivity in young mice and led to lasting memory deficits in the object recognition test and greater ethanol sensitivity in adulthood. Using genomic profiling of transcripts in the PFC, we found that binge ethanol reduced myelin-related gene expression and altered chromatin modifying genes involved in histone demethylation at H3K9 and H3K36. We hypothesize that ethanol's actions on histone methylation may be a switch for future transcriptional changes that underlie the behavioral changes lasting into adulthood.

Citing Articles

Adolescent binge ethanol impacts H3K9me3-occupancy at synaptic genes and the regulation of oligodendrocyte development.

Brocato E, Easter R, Morgan A, Kakani M, Lee G, Wolstenholme J Front Mol Neurosci. 2024; 17:1389100.

PMID: 38840776 PMC: 11150558. DOI: 10.3389/fnmol.2024.1389100.

Voluntary adolescent alcohol exposure does not robustly increase adulthood consumption of alcohol in multiple mouse and rat models.

Sicher A, Liss A, Vozella V, Marsland P, Seemiller L, Springer M bioRxiv. 2024; .

PMID: 38746266 PMC: 11092607. DOI: 10.1101/2024.04.30.591674.

Adolescent alcohol and nicotine exposure alters the adult response to alcohol use.

Hauser S, Waeiss R, Deehan Jr G, Engleman E, Bell R, Rodd Z Adv Drug Alcohol Res. 2024; 3:11880.

PMID: 38389816 PMC: 10880795. DOI: 10.3389/adar.2023.11880.

Adolescent social housing protects against adult emotional and cognitive deficits and alters the PFC and NAc transcriptome in male and female C57BL/6J mice.

Lodha J, Brocato E, Nash M, Marcus M, Pais A, Pais A Front Neurosci. 2023; 17:1287584.

PMID: 38130694 PMC: 10733512. DOI: 10.3389/fnins.2023.1287584.

HMGB1 neuroimmune signaling and REST-G9a gene repression contribute to ethanol-induced reversible suppression of the cholinergic neuron phenotype.

Crews F, Fisher R, Qin L, Vetreno R Mol Psychiatry. 2023; 28(12):5159-5172.

PMID: 37402853 PMC: 10764639. DOI: 10.1038/s41380-023-02160-6.

References

Coleman Jr L, Liu W, Oguz I, Styner M, Crews F . Adolescent binge ethanol treatment alters adult brain regional volumes, cortical extracellular matrix protein and behavioral flexibility. Pharmacol Biochem Behav. 2013; 116:142-51. PMC: 3913047. DOI: 10.1016/j.pbb.2013.11.021. View

Lee K, Coelho M, McGregor H, Solton N, Cohen M, Szumlinski K . Adolescent Mice Are Resilient to Alcohol Withdrawal-Induced Anxiety and Changes in Indices of Glutamate Function within the Nucleus Accumbens. Front Cell Neurosci. 2016; 10:265. PMC: 5114265. DOI: 10.3389/fncel.2016.00265. View

Lehnertz B, Ueda Y, Derijck A, Braunschweig U, Perez-Burgos L, Kubicek S . Suv39h-mediated histone H3 lysine 9 methylation directs DNA methylation to major satellite repeats at pericentric heterochromatin. Curr Biol. 2003; 13(14):1192-200. DOI: 10.1016/s0960-9822(03)00432-9. View

Heilig M, Barbier E, Johnstone A, Tapocik J, Meinhardt M, Pfarr S . Reprogramming of mPFC transcriptome and function in alcohol dependence. Genes Brain Behav. 2016; 16(1):86-100. PMC: 5555395. DOI: 10.1111/gbb.12344. View

Antunes M, Biala G . The novel object recognition memory: neurobiology, test procedure, and its modifications. Cogn Process. 2011; 13(2):93-110. PMC: 3332351. DOI: 10.1007/s10339-011-0430-z. View

Liu J, Lewohl J, Dodd P, Randall P, Harris R, Mayfield R . Gene expression profiling of individual cases reveals consistent transcriptional changes in alcoholic human brain. J Neurochem. 2004; 90(5):1050-8. DOI: 10.1111/j.1471-4159.2004.02570.x. View

Wolstenholme J, Warner J, Capparuccini M, Archer K, Shelton K, Miles M . Genomic analysis of individual differences in ethanol drinking: evidence for non-genetic factors in C57BL/6 mice. PLoS One. 2011; 6(6):e21100. PMC: 3116881. DOI: 10.1371/journal.pone.0021100. View

Grant B, Dawson D . Age at onset of alcohol use and its association with DSM-IV alcohol abuse and dependence: results from the National Longitudinal Alcohol Epidemiologic Survey. J Subst Abuse. 1997; 9:103-10. DOI: 10.1016/s0899-3289(97)90009-2. View

Dudek B, Phillips T, Hahn M . Genetic analyses of the biphasic nature of the alcohol dose-response curve. Alcohol Clin Exp Res. 1991; 15(2):262-9. DOI: 10.1111/j.1530-0277.1991.tb01867.x. View

10.

Pascual M, Do Couto B, Alfonso-Loeches S, Aguilar M, Rodriguez-Arias M, Guerri C . Changes in histone acetylation in the prefrontal cortex of ethanol-exposed adolescent rats are associated with ethanol-induced place conditioning. Neuropharmacology. 2012; 62(7):2309-19. DOI: 10.1016/j.neuropharm.2012.01.011. View

11.

Zhang L, Wang L, Ravindranathan A, Miles M . A new algorithm for analysis of oligonucleotide arrays: application to expression profiling in mouse brain regions. J Mol Biol. 2002; 317(2):225-35. DOI: 10.1006/jmbi.2001.5350. View

12.

Morais-Silva G, Fernandes-Santos J, Moreira-Silva D, Marin M . Concomitant stress potentiates the preference for, and consumption of, ethanol induced by chronic pre-exposure to ethanol. Braz J Med Biol Res. 2015; 49(1):e5009. PMC: 4681418. DOI: 10.1590/1414-431X20155009. View

13.

Wise R, Bozarth M . A psychomotor stimulant theory of addiction. Psychol Rev. 1987; 94(4):469-92. View

14.

Kroenke C, Rohlfing T, Park B, Sullivan E, Pfefferbaum A, Grant K . Monkeys that voluntarily and chronically drink alcohol damage their brains: a longitudinal MRI study. Neuropsychopharmacology. 2013; 39(4):823-30. PMC: 3924514. DOI: 10.1038/npp.2013.259. View

15.

Luciana M, Collins P, Muetzel R, Lim K . Effects of alcohol use initiation on brain structure in typically developing adolescents. Am J Drug Alcohol Abuse. 2013; 39(6):345-55. PMC: 4076828. DOI: 10.3109/00952990.2013.837057. View

16.

Crews F, Mdzinarishvili A, Kim D, He J, Nixon K . Neurogenesis in adolescent brain is potently inhibited by ethanol. Neuroscience. 2005; 137(2):437-45. DOI: 10.1016/j.neuroscience.2005.08.090. View

17.

Costin B, Wolen A, Fitting S, Shelton K, Miles M . Role of adrenal glucocorticoid signaling in prefrontal cortex gene expression and acute behavioral responses to ethanol. Alcohol Clin Exp Res. 2012; 37(1):57-66. PMC: 3507324. DOI: 10.1111/j.1530-0277.2012.01841.x. View

18.

Barbier E, Johnstone A, Khomtchouk B, Tapocik J, Pitcairn C, Rehman F . Dependence-induced increase of alcohol self-administration and compulsive drinking mediated by the histone methyltransferase PRDM2. Mol Psychiatry. 2016; 22(12):1746-1758. PMC: 5677579. DOI: 10.1038/mp.2016.131. View

19.

Gorin-Meyer R, Wiren K, Tanchuck M, Long S, Yoneyama N, Finn D . Sex differences in the effect of finasteride on acute ethanol withdrawal severity in C57BL/6J and DBA/2J mice. Neuroscience. 2007; 146(3):1302-15. PMC: 1963463. DOI: 10.1016/j.neuroscience.2007.02.051. View

20.

Chen J, Bardes E, Aronow B, Jegga A . ToppGene Suite for gene list enrichment analysis and candidate gene prioritization. Nucleic Acids Res. 2009; 37(Web Server issue):W305-11. PMC: 2703978. DOI: 10.1093/nar/gkp427. View