Increased activation of synapsin 1 and mitogen-activated protein kinases/extracellular signal-regulated kinase in the amygdala of maternal separation rats

摘要

Background: Early life stress (ELS) causes alterations in emotionality and anxiety levels as a significant risk factor for psychiatric problems, and these alterations have been associated with amygdala activity. Aims: To elucidate the molecular mechanism on the development of psychiatric problems following ELS, we identified the alteration of molecules in the amygdala using maternal separation (MS; pnd 14-21) rats through gene expression and DNA methylation microarray analysis, and studied the involvement of candidate genes using a Western blot and immunohistochemistry analysis. Results: Through a microarray analysis, in the amygdala of MS rats, we found a downregulation of mRNA expression of synapsin 1 (Syn1) gene with hypermethylation of its transcription start site (TSS), and the alterations of mRNA expressions of Syn1 activation-related kinase genes including mitogen-activated protein kinases (Mapks) with change of their TSS methylation. In addition, MS increased not only Syn1 phosphorylation at the phosphorylation sites by Mapk/extracellular signal-regulated kinase (Erk), but also Mapk/Erk phosphorylation in the amygdala. Furthermore, double immunofluorescence staining showed that MS could elevate phospho-Mapk/Erk immunoreactivity (IR) in Syn1-expression puncta. Conclusion: These findings indicated that the activation of Mapk/Erk and Syn1 may be a key mechanism modulating synaptic neurotransmition in the amygdala of MS rats.