A role for histone acetylation mechanisms in adolescent alcohol exposure-induced deficits in hippocampal brain-derived neurotrophic factor expression and neurogenesis markers in adulthood

Amul J. Sakharkar, Ryan P. Vetreno, Huaibo Zhang, Dadasaheb M. Kokare, Fulton T. Crews, Subhash C. Pandey

Research output: Contribution to journalArticle

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Abstract

Binge drinking during adolescence is a risk factor for neuropsychiatric disorders that can develop later in life. Histone acetylation is an important epigenetic mechanism that contributes to neurodevelopment. We investigated the effects of adolescent intermittent ethanol (AIE) exposure, as opposed to normal saline (AIS) exposure, on histone acetylation-mediated regulation of brain-derived neurotrophic factor (BDNF) expression and developmental stages of neurogenesis (proliferating and immature neurons) in the hippocampus in adulthood. AIE exposure increased whole hippocampal histone deacetylase (HDAC) activity and decreased binding protein of cyclic adenosine monophosphate response element binding protein (CBP) and histone H3-K9 acetylation levels in the CA1, CA2, and CA3 regions of the hippocampus. BDNF protein and exon IV mRNA levels in the CA1 and CA3 regions of the hippocampus of AIE-exposed adult rats were decreased as compared to AIS-exposed adult rats. AIE-induced anxiety-like behaviors and deficits in histone H3 acetylation at BDNF exon IV promoter in the hippocampus during adulthood, which were reversed by treatment with the HDAC inhibitor, trichostatin A (TSA). Similarly, neurogenesis was inhibited by AIE in adulthood as demonstrated by the decrease in Ki-67 and doublecortin (DCX)-positive cells in the dentate gyrus, which was normalized by TSA treatment. These results indicate that AIE exposure increases HDACs and decreases CBP levels that may be associated with a decrease in histone H3 acetylation in the hippocampus. These epigenetic changes potentially decrease BDNF expression and inhibit neurogenesis in the hippocampus that may be involved in AIE-induced behavioral abnormalities, including anxiety, in adulthood.

LanguageEnglish (US)
Pages4691-4703
Number of pages13
JournalBrain Structure and Function
Volume221
Issue number9
DOIs
StatePublished - Dec 1 2016

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Brain-Derived Neurotrophic Factor
Neurogenesis
Acetylation
Histones
Alcohols
Ethanol
Hippocampus
trichostatin A
Epigenomics
Exons
Carrier Proteins
Anxiety
Binge Drinking
Histone Deacetylase Inhibitors
Histone Deacetylases
Dentate Gyrus
Nerve Growth Factors
Response Elements
Cyclic AMP
Neurons

Keywords

  • Adolescent alcohol
  • Anxiety
  • Brain-derived neurotrophic factor
  • Hippocampus
  • Histone H3 acetylation
  • Neurogenesis

ASJC Scopus subject areas

  • Anatomy
  • Neuroscience(all)
  • Histology

Cite this

A role for histone acetylation mechanisms in adolescent alcohol exposure-induced deficits in hippocampal brain-derived neurotrophic factor expression and neurogenesis markers in adulthood. / Sakharkar, Amul J.; Vetreno, Ryan P.; Zhang, Huaibo; Kokare, Dadasaheb M.; Crews, Fulton T.; Pandey, Subhash C.

In: Brain Structure and Function, Vol. 221, No. 9, 01.12.2016, p. 4691-4703.

Research output: Contribution to journalArticle

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