Adolescent Binge-Type Ethanol Exposure in Rats Mirrors Age-Related Cognitive Decline by Suppressing Cholinergic Tone and Hippocampal Neurogenesis

Abstract

Heavy alcohol consumption followed by periods of abstinence (i.e., binge drinking) during adolescence is a concern for both acute and chronic health issues. Persistent brain damage after adolescent intermittent ethanol exposure in rodents, a model of binge drinking, includes reduced hippocampal neurogenesis and a loss of neurons in the basal forebrain that express the cholinergic phenotype. The circuit formed between those regions, the septohippocampal pathway, is critical for learning and memory. Furthermore, this circuit is also altered during the aging process. Thus, we examined whether pathology in septohippocampal circuit and impairments in spatial behaviors are amplified during aging following adolescent intermittent ethanol exposure. Female and male rats were exposed to intermittent intragastric gavage of water (control) or 20% ethanol (dose of 5 g/kg) for a 2 days on/off cycle from postnatal days 25–55. Either 2 (young adult) or 12–14 (middle-age) months post exposure, rats were tested on two spatial tasks: spontaneous alternation and novel object in place. Acetylcholine efflux was assessed in the hippocampus during both tasks. There was no adolescent ethanol-induced deficit on spontaneous alternation, but middle-aged male rats displayed lower alternation rates. Male rats exposed to ethanol during adolescence had blunted behavioral evoked acetylcholine during spontaneous alternation testing. All ethanol-exposed rats displayed suppression of the cholinergic neuronal phenotype. On the novel object in place task, regardless of sex, ethanol-exposed rats performed significantly worse than control-treated rats, and middle aged-rats, regardless of sex or ethanol exposure, were significantly impaired relative to young adult rats. These results indicate that male rats display earlier age-related cognitive impairment on a working memory task. Furthermore, male rats exposed to ethanol during adolescence have blunted behavior-evoked hippocampal acetylcholine efflux. In addition, middle-aged and ethanol-exposed rats, regardless of sex, are impaired at determining discrete spatial relationship between objects. This type of pattern separation impairment was associated with a loss of neurogenesis. Thus, binge-type adolescent ethanol exposure does affect the septohippocampal circuit, and can accelerate age-related cognitive impairment on select spatial tasks.

Patterns of Alcohol Consumption and Associated Factors in a Population-Based Sample of 70-Year-Olds: Data from the Gothenburg H70 Birth Cohort Study 2014–16

“…Overall, recent pre-clinical research has found that excessive alcohol exposure during adolescence may increase the risk of chronic health issues, especially in terms of brain damage [ 57 , 58 ]. Unfortunately, we have no information about the consumption pattern during adolescence.…”

Neuroprotective activity of Conyza aegyptiaca hydroethanolic extract against ethanol-induced neurodegeneration in adolescent Wistar rats brain

“…The review of Crews and Nixon (2009) described well preclinical rat experiments using a 4-day binge ethanol treatment known to induce brain damages. Binge drinking is defined as heavy alcohol consumption followed by periods of abstinence during adolescence (Reitz et al, 2021). In this model, the peak of neurodegeneration generally occurs on the 3rd day after the animals have received ethanol (Crews and Nixon, 2009).…”

Prenatal methadone exposure leads to long-term memory impairments and disruptions of dentate granule cell function in a sex-dependent manner

“…1,3,2,4). Percent alternation scores were calculated as ((number of alternations/ (total number of arm entries – 3)) *100), as previously described 26,27…”

“…Adult offspring (P70-120; n = 5-7 per group, per sex across 2-5 litters per group) were briefly sedated with 3% isoflurane and quickly decapitated. Brains were rapidly removed and immersed in ice cold oxygenated (95% O2, 5% CO2) sucrose artificial cerebrospinal fluid (ACSF) cutting solution containing (in mM): sucrose (220), KCl (2), NaH2PO4 (1.3), NaHCO3 (26), glucose (10), MgSO4 (12), CaCl2 (0.2), and ketamine (0.43). 300 µm brain slices containing the dorsal hippocampus were made using a Vibratome (Leica Microsystems, Bannockburn, IL, USA).…”

“…300 µm brain slices containing the dorsal hippocampus were made using a Vibratome (Leica Microsystems, Bannockburn, IL, USA). Slices were incubated in oxygenated ACSF containing (in mM): NaCl (125), KCl (2), NaH2PO4 (1.3), NaHCO3 (26), glucose (10), CaCl2 (2), MgSO4 (1), and ascorbic acid (0.4), and allowed to recover for at least 40 min at 34°C before recording. Slices remained at 34°C, and all experiments were performed within 5 hours of slice preparation.…”