ArticleAlcohol, clinical & experimental research2023
Indomethacin restores loss of hippocampal neurogenesis and cholinergic innervation and reduces innate immune expression and reversal learning deficits in adult male and female rats following adolescent ethanol exposure.
Article in Alcohol, clinical & experimental research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 11 citations in OpenAlex.
- Adolescent Ethanol Exposure Disrupts the Mature Phenotype of Surviving Neuroprogenitors in Female Mice.Hippocampus · 2026Article
- Epigenetic Repression of the Serotonergic Neuron Phenotype Following Adolescent Binge Drinking Is Restored through Inhibition of Proinflammatory Signaling by Exercise and Glycyrrhizic Acid.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Article
- Adolescent binge alcohol exposure accelerates Alzheimer's disease-associated basal forebrain neuropathology through proinflammatory HMGB1 signaling.Frontiers in aging neuroscience · 2025Article
- Adolescent Alcohol and the Spectrum of Cognitive Dysfunction in Aging.Advances in experimental medicine and biology · 2025Review
- Epigenetic regulation of microglia and neurons by proinflammatory signaling following adolescent intermittent ethanol (AIE) exposure and in human AUD.Advances in drug and alcohol research · 2024Review
- HMGB1 neuroimmune signaling and REST-G9a gene repression contribute to ethanol-induced reversible suppression of the cholinergic neuron phenotype.Molecular psychiatry · 2023Article
- Review
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
backgroundAdolescent intermittent ethanol (AIE) exposure causes long-term changes in the brain and behavior of adult male rodents, including persistent induction of innate immune pathways, reductions in hippocampal neurogenic and forebrain cholinergic neuronal markers, and reversal learning deficits. The current study tests the hypothesis that proinflammatory induction mediates AIE-induced (1) loss of adult neurogenesis (i.e., doublecortin (DCX) expressing immature neurons), (2) reductions in forebrain and hippocampal cholinergic markers, and (3) reversal learning deficits.
methodsMale and female rats underwent AIE (5.0 g/kg/day ethanol or water, i.g., 2 day-on/2 day-off from postnatal day (PND) 25-54), followed by a 2-week regimen of the anti-inflammatory compound indomethacin (4.0 g/kg/day, PND 56-69) or vehicle, after which one cohort was euthanized for immunohistochemical markers (PND 70) and the second underwent the Morris water maze to assess reversal learning.
resultsAIE reduced adult (PND 70) DCX+ immunoreactivity (IR) and increased hippocampal expression of the innate immune signal's high-mobility group box protein 1 (HMGB1 + IR) and cyclooxygenase-2 (COX-2 + IR) in adult male and female rats. AIE also reduced choline acetyltransferase (ChAT+IR) in the basal forebrain and co-labeling of hippocampal vesicular acetylcholine transporter (VAChT+) cholinergic terminals on DCX + IR neurons. Indomethacin treatment after AIE restored molecular endpoints to control levels and rescued AIE-induced reversal learning deficits in the Morris water maze in both sexes. Of note, indomethacin produced several adverse effects selectively in control conditions, highlighting the uniquely beneficial effect of indomethacin in AIE rats.
conclusionsThese data suggest that in males and females, (1) AIE persistent neuroimmune induction mediates both the loss of adult hippocampal DCX and loss of basal forebrain cholinergic neurons and their innervation to hippocampal targets, and (2) anti-inflammatory indomethacin treatment following AIE that restores these persistent molecular pathologies also restores spatial reversal learning deficits.
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