N-acetyl Cysteine Reduces Behavioral Disorders of the First and Second-generation Weaned Mice through the Modulation of TAC and the DNMT1 Gene Expression in the Hippocampus.

INTRODUCTION

This research aimed to reveal the role of antioxidants and DNMT1 gene expression in behavioral disorders after exposure to stress.

METHODS

Forty-eight male and female mice (weight 25-35 grams) were used. Their pups (weight 18-22 grams) were divided into 6 groups (n=20), Control, Social isolation stress (SIS), and SIS + N-acetylcysteine (NAC) 150 mg/kg intraperitoneally for male and 3 similar groups for female subjects, eight mice from each group were used for the first-generation experiments and another for mating and producing the second generation. The second-generation pups were designated into 9 groups A to I. After conducting behavioral tests of the Morris water maze (MWM) and shuttle box, they were anesthetized, decapitated, and their brains were removed. The neuronal counts of CA1 and CA3 were performed. DNMT1 gene expression, total antioxidant capacity (TAC), and malondialdehyde (MDA) of the brain were measured.

RESULTS

Spatial memory, passive avoidance, and TAC decreased in the SIS groups. MDA and DNMT1 gene expression of the SIS groups increased (p<0.001). Dead neurons in the CA1 and CA3 regions increased in the SIS group (p<0.001).

DISCUSSION: According to the results of this study, N-acetylcysteine enhanced learning and memory while reducing neuronal death by decreasing oxidative stress. Additionally, it lowered the expression of the DNMT1 gene, which plays a crucial role in DNA methylation.

CONCLUSION

After studying the human population, N-acetylcysteine may be introduced as an adjunct therapy to help mitigate the effects of stress.