1. ISRIB ameliorates spatial learning and memory impairment induced by adolescent intermittent ethanol exposure in adult male rats.
- Author
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Jia W, Li C, Chen H, Wang X, Liu Y, Shang W, Wang B, Meng W, Guo Y, Zhu L, Wang D, Zhou D, Zhao B, and Wei L
- Subjects
- Animals, Male, Rats, Prefrontal Cortex drug effects, Prefrontal Cortex metabolism, Endoplasmic Reticulum Stress drug effects, Hippocampus drug effects, Hippocampus metabolism, Maze Learning drug effects, Maze Learning physiology, Ethanol toxicity, Ethanol administration & dosage, Memory Disorders chemically induced, Memory Disorders drug therapy, Memory Disorders metabolism, Spatial Learning drug effects, Rats, Sprague-Dawley
- Abstract
Alcohol exposure in adolescence is considered a major cause of cognitive impairments later in life including spatial learning and memory. Integrated stress response (ISR), a program of conservative translation and transcription, is crucial in synaptic plasticity and memory. Although previous studies have elucidated ISR in different brain areas involved in learning and memory disorders, the impact of ISR on learning and memory following adolescent alcohol exposure remains unclear. Here, we demonstrated that adolescent intermittent ethanol (AIE) exposure caused spatial learning and memory impairment, combined with neuronal damage in the medial prefrontal cortex (mPFC), nucleus accumbens (NAc) and hippocampus (HIP) in adult rats. Moreover, integrated stress response inhibitor (ISRIB) administration not only improved spatial learning and memory impairment and neuronal damage but also inhibited the endoplasmic reticulum stress (ER) and reversed changes in synaptic proteins. These findings suggested that ISRIB ameliorates AIE exposure-induced spatial learning and memory deficits by improving neural morphology and synaptic function through inhibiting ER stress signaling pathway in the mPFC, NAc and HIP in adulthood. Our findings may enhance comprehension of cognitive function and neuronal effects of adolescent ethanol exposure and ISRIB treatment may be an underlying potential option for addressing alcohol-induced learning and memory deficits., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
- Published
- 2024
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