dc.description.abstract | Stress is known to increase the risk of mental illness. Previous studies have shown that stress affects both neuronal mechanisms in the brain and behavior. Observational fear, the process of learning fear through others, helps individuals adapt to negative stimuli, and its impairment is a common symptom in patients with mental illness. In our preliminary data, we found that male DS-Ob mice exhibited reduced freezing time during observational fear learning
test and decreased neural activity in the amygdala. However, the underlying mechanisms linking stress and observational fear learning remain unclear. In this study, we used a male
stressed-mice model to investigate this mechanism. We first performed RNA sequencing on the amygdala of each stressed mouse and found that 81 differentially expression genes were
downregulated in male DS-Ob mice. Gene Ontology (GO) analysis indicated that these genes are involved in myelin sheath formation and glial cell function, including genes such as Cntn2 and Sgpp2. Furthermore, we examined the mRNA expression of myelin-related genes in the amygdala of stressed male mice using qPCR, which revealed decreased expression of these genes in male DS-Ob mice. Given that serotonin, oxytocin and dopamine systems are frequently
implicated in mental illness, we also identified these systems in our RNA sequencing data as being related to doubled-stress and observational fear learning.Specifically, we found that the expression of CD38 decreased, while Oxt and SLC6A4 increased in male DS-Ob mice, as confirmed by qPCR. To determine whether these genes are involved in both doubled-stress and observational fear learning, we compared mRNA expression levels between Naïve and OFL groups, with or without doubled-stress. Our results showed that Sgpp2 and CD38 decreased, while Oxt and SLC6A4 increased after doubled-stress and observational fear learning in the amygdala of male mice. In summary, this thesis demonstrates that myelination, serotonin, and oxytocin systems in the amygdala play a role in regulating doubled-stress and observational fear learning in male mice. These findings offer new insights into the mechanisms underlying observational fear learning impairment in stress-induced mental illness disorders. | en_US |