Increased Activation of Synapsin 1 and Mitogen-Activated Protein Kinases/Extracellular Signal-Regulated Kinase in the Amygdala of Maternal Separation Rats




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.


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.


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.


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.