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Introduction <p>Autism spectrum disorders (ASD) include a&#xa0;complex set of behavioral disabilities stemming from genetic and environmental factors, such as prenatal exposure to valproic acid (VPA). Autism impacts social and cognitive domains, with varying severity and symptoms depending on age and individual differences. The study examined the effects of environmental stress, such as maternal deprivation, and VPA administration on learning and memory in autistic rats.</p> Methods <p>Eight groups of animals were studied (male and female separately): 0.9% saline control, VPA (300 mg on Days&#xa0;2–4), maternal deprivation (120 min on Days&#xa0;2, 3, and&#xa0;5), and the combination of VPA + maternal deprivation. After treatment, behavioral tests including Morris Water Maze and shuttle box tests were conducted to evaluate learning and memory in the offspring. Tests were performed 30,&#xa0;31, and 34&#xa0;days after birth. Brain total antioxidant capacity (TAC) and malondialdehyde (MDA) levels were measured as markers of oxidative stress.</p> Results <p>In the Morris Water Maze test, VPA injection and maternal deprivation significantly affected time elapsed and distance traveled indices in both male and female offspring. There was no substantial difference between groups in time and distance to reach the platform. Maternal deprivation in males increased the time and distance needed to reach the platform. In the shuttle box test, avoidance memory was reduced in male and female offspring across therapeutic trials, with no significant difference between treatment groups. Biochemically, VPA and MD alone or in combination significantly decreased brain TAC and increased MDA levels, indicating oxidative stress. The VPA + MD group showed the most pronounced oxidative damage, which paralleled the greatest cognitive deficits.</p> Conclusion <p>VPA injections impaired spatial learning and memory but did not affect avoidance memory. The accompanying reduction in TAC and elevation in MDA suggest that oxidative stress mediates, at least in part, the cognitive deficits induced by postnatal VPA and maternal deprivation.</p>

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Spatial cognition and avoidance memory disruption after postnatal valproic acid exposure and early maternal deprivation in ASD rat model

  • 期刊论文

  • 发表日期：

    2025年4月1日

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  • Ali Kosari,
  • Marjan Mahmoodabadi,
  • Sina Delshad,
  • Sara Sheibani Tezerji,
  • Azadeh Aminzadeh,
  • Mahmoud Reza Heidari,
  • Hamideh Bashiri

摘要

Introduction

Autism spectrum disorders (ASD) include a complex set of behavioral disabilities stemming from genetic and environmental factors, such as prenatal exposure to valproic acid (VPA). Autism impacts social and cognitive domains, with varying severity and symptoms depending on age and individual differences. The study examined the effects of environmental stress, such as maternal deprivation, and VPA administration on learning and memory in autistic rats.

Methods

Eight groups of animals were studied (male and female separately): 0.9% saline control, VPA (300 mg on Days 2–4), maternal deprivation (120 min on Days 2, 3, and 5), and the combination of VPA + maternal deprivation. After treatment, behavioral tests including Morris Water Maze and shuttle box tests were conducted to evaluate learning and memory in the offspring. Tests were performed 30, 31, and 34 days after birth. Brain total antioxidant capacity (TAC) and malondialdehyde (MDA) levels were measured as markers of oxidative stress.

Results

In the Morris Water Maze test, VPA injection and maternal deprivation significantly affected time elapsed and distance traveled indices in both male and female offspring. There was no substantial difference between groups in time and distance to reach the platform. Maternal deprivation in males increased the time and distance needed to reach the platform. In the shuttle box test, avoidance memory was reduced in male and female offspring across therapeutic trials, with no significant difference between treatment groups. Biochemically, VPA and MD alone or in combination significantly decreased brain TAC and increased MDA levels, indicating oxidative stress. The VPA + MD group showed the most pronounced oxidative damage, which paralleled the greatest cognitive deficits.

Conclusion

VPA injections impaired spatial learning and memory but did not affect avoidance memory. The accompanying reduction in TAC and elevation in MDA suggest that oxidative stress mediates, at least in part, the cognitive deficits induced by postnatal VPA and maternal deprivation.