Changes in Neuroimmune and Neuronal Death Markers after Adolescent Alcohol Exposure in Rats are Reversed by Donepezil
Autor: | Kira Dubester, Fulton T. Crews, Kati L. Healey, Kelsey M. Miller, H. S. Swartzwelder, Wen Liu |
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Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
medicine.medical_specialty Dendritic spine Doublecortin Protein Dendritic Spines Neurogenesis lcsh:Medicine Underage Drinking HMGB1 Hippocampus Methylation Article Epigenesis Genetic 03 medical and health sciences 0302 clinical medicine Internal medicine mental disorders Medicine Animals Humans Donepezil lcsh:Science Cholinesterase Progenitor Inflammation Multidisciplinary biology Cell Death Ethanol business.industry Dentate gyrus lcsh:R Acetylation 3. Good health Doublecortin Rats Disease Models Animal 030104 developmental biology Endocrinology Neurology Dentate Gyrus biology.protein lcsh:Q business 030217 neurology & neurosurgery medicine.drug Neuroscience |
Zdroj: | Scientific Reports Scientific Reports, Vol 9, Iss 1, Pp 1-12 (2019) |
ISSN: | 2045-2322 |
Popis: | 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. |
Databáze: | OpenAIRE |
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