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N-Acetylcysteine Modulates ATF4 Methylation to Alleviate Cognitive Impairments in PTSD Mice
  • Yanling Zhou,
  • Min Guo,
  • Xiuhong Yuan
Yanling Zhou
The Fourth People's Hospital of Haikou
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Min Guo
Hainan General Hospital

Corresponding Author:[email protected]

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Xiuhong Yuan
Central South University Xiangya School of Medicine Affiliated Haikou Hospital
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Abstract

Post-traumatic stress disorder (PTSD) often results in significant cognitive impairments and neuronal apoptosis, presenting a critical challenge for effective therapeutic intervention. This study explores the potential of N-acetylcysteine (NAC) in ameliorating PTSD-induced cognitive dysfunction and neuronal damage in a mouse model, with a specific focus on the modulation of activating transcription factor 4 (ATF4) expression and its m6A RNA methylation. Using the single prolonged stress (SPS) model to induce PTSD-like symptoms, mice were administered NAC and subsequently subjected to Morris water maze and open field tests to assess cognitive performance. Immunohistochemistry, Western blot, and enzyme assays were employed to evaluate neuronal apoptosis in the hippocampus. Methylation-specific RNA immunoprecipitation and qRT-PCR were used to analyze the regulation of ATF4 expression and m6A methylation. Results demonstrated that NAC treatment significantly improved cognitive function and reduced hippocampal neuronal apoptosis. These effects were closely associated with decreased m6A methylation levels and reduced expression of ATF4. Silencing of ATF4 further diminished neuronal apoptosis and cognitive impairments, underscoring the crucial role of ATF4 methylation in PTSD pathology. This study highlights the therapeutic potential of NAC in PTSD, revealing a novel mechanism through the modulation of ATF4 methylation, and paving the way for innovative treatment strategies.
28 Jul 2024Submitted to European Journal of Neuroscience
29 Jul 2024Submission Checks Completed
29 Jul 2024Assigned to Editor
29 Jul 2024Review(s) Completed, Editorial Evaluation Pending
31 Jul 2024Reviewer(s) Assigned
02 Oct 2024Editorial Decision: Revise Major