Skip to main content

Changes in Neuroimmune and Neuronal Death Markers after Adolescent Alcohol Exposure in Rats are Reversed by Donepezil.

Publication ,  Journal Article
Swartzwelder, HS; Healey, KL; Liu, W; Dubester, K; Miller, KM; Crews, FT
Published in: Sci Rep
August 20, 2019

Adolescent intermittent ethanol (AIE) exposure diminishes neurogenesis and dendritic spine density in the dentate gyrus. The cholinesterase inhibitor, donepezil (Aricept), reverses AIE effects on dendritic spines, possibly by interacting with inflammatory and/or epigenetic mediators after AIE exposure. This study tests the hypothesis that donepezil reverses AIE-induced neuroimmune, and epigenetic changes in the adult dentate gyrus. Adolescent Sprague-Dawley male rats (PD30-43) were given 10 intermittent, intragastric doses of ethanol (5.0 g/kg) or isovolumetric water (AIW). Twenty-one days later half of the animals from each group were treated with either donepezil or isovolumetric water (i.g.) once daily for four days. Two hours after the last donepezil or water dose animals were sacrificed and brains prepared for immunohistochemical analyses. AIE reduced immunoreactivity for doublecortin (DCX) and increased immunoreactivity for activated caspase-3 and death receptor-3 in adulthood, suggesting an enduring attenuation of neurogenesis and an increase in progenitor death. These effects were reversed by donepezil treatment in adulthood. AIE also increased immunoreactivity for the inflammatory signaling molecules HMGB1 and RAGE, as well as the activated phosphorylated transcription factor pNFκB p65, and the gene silencing marker dimethylated histone H3K9. All of these AIE effects were also reversed by donepezil, with the exception of HMGB1.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Sci Rep

DOI

EISSN

2045-2322

Publication Date

August 20, 2019

Volume

9

Issue

1

Start / End Page

12110

Location

England

Related Subject Headings

  • Underage Drinking
  • Rats
  • Neurogenesis
  • Methylation
  • Inflammation
  • Humans
  • Hippocampus
  • Ethanol
  • Epigenesis, Genetic
  • Doublecortin Protein
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Swartzwelder, H. S., Healey, K. L., Liu, W., Dubester, K., Miller, K. M., & Crews, F. T. (2019). Changes in Neuroimmune and Neuronal Death Markers after Adolescent Alcohol Exposure in Rats are Reversed by Donepezil. Sci Rep, 9(1), 12110. https://doi.org/10.1038/s41598-019-47039-1
Swartzwelder, H. S., Kati L. Healey, Wen Liu, Kira Dubester, Kelsey M. Miller, and Fulton T. Crews. “Changes in Neuroimmune and Neuronal Death Markers after Adolescent Alcohol Exposure in Rats are Reversed by Donepezil.Sci Rep 9, no. 1 (August 20, 2019): 12110. https://doi.org/10.1038/s41598-019-47039-1.
Swartzwelder HS, Healey KL, Liu W, Dubester K, Miller KM, Crews FT. Changes in Neuroimmune and Neuronal Death Markers after Adolescent Alcohol Exposure in Rats are Reversed by Donepezil. Sci Rep. 2019 Aug 20;9(1):12110.
Swartzwelder, H. S., et al. “Changes in Neuroimmune and Neuronal Death Markers after Adolescent Alcohol Exposure in Rats are Reversed by Donepezil.Sci Rep, vol. 9, no. 1, Aug. 2019, p. 12110. Pubmed, doi:10.1038/s41598-019-47039-1.
Swartzwelder HS, Healey KL, Liu W, Dubester K, Miller KM, Crews FT. Changes in Neuroimmune and Neuronal Death Markers after Adolescent Alcohol Exposure in Rats are Reversed by Donepezil. Sci Rep. 2019 Aug 20;9(1):12110.

Published In

Sci Rep

DOI

EISSN

2045-2322

Publication Date

August 20, 2019

Volume

9

Issue

1

Start / End Page

12110

Location

England

Related Subject Headings

  • Underage Drinking
  • Rats
  • Neurogenesis
  • Methylation
  • Inflammation
  • Humans
  • Hippocampus
  • Ethanol
  • Epigenesis, Genetic
  • Doublecortin Protein