DNA methylation regulates the extinction of fear memory.

BACKGROUND: Fear-related disorders, such as post-traumatic stress disorder (PTSD), significantly impact patients and families. Exposure therapy is a common treatment, but improving its effectiveness remains a key challenge. Fear conditioning and extinction in animal models offer insights into its mechanisms. Our previous research indicates that DNA methyltransferases play a role in fear memory renewal. AIM: To investigate the role of DNA methylation in the extinction of fear memory, with the goal of identifying potential strategies to enhance the efficacy of exposure therapy for fear-related disorders. METHODS: This study investigated the role of DNA methylation in fear memory extinction in mice. DNA methylation was manipulated using N-phthalyl-L-tryptophan (RG108) to reduce methylation and L-methionine injections to enhance it. Neuronal activity, and dendritic spine density was measured following extinction training. RESULTS: RG108 suppressed extinction, reduced spine density, and inhibited neuronal activity. Methionine injections facilitated extinction. CONCLUSION: DNA methylation is crucial for fear memory extinction. Enhancing methylation may improve the efficacy of exposure therapy, offering a potential strategy to treat fear-related disorders.