Anxiety disorder is a major psychiatric disorder characterized by fear, worry, and excessive rumination. However, the molecular mechanisms underlying neural plasticity and anxiety remain unclear. Here, we utilized a mouse model of anxiety-like behaviors induced by the chronic administration of corticosterone (CORT) to determine the exact mechanism of each region of the fear circuits in the anxiety disorders. Chronic CORT-treated mice showed a significant increase in anxiety-related behaviors as assessed by the elevated plus maze, light–dark, open-field, and marble-burying tasks. In addition, chronic CORT-treated mice exhibited abnormal amygdala-dependent tone-induced fear memory but normal hippocampus-dependent contextual memory. Consistent with amygdala hyperactivation, chronic CORT-treated mice showed significantly increased numbers of c-Fos-positive cells in the basolateral amygdala (BLA) after tone stimulation. Long-term potentiation (LTP) was markedly enhanced in the BLA of chronic CORT-treated mice compared to that of vehicle-treated mice. Immunoblot analyses revealed that autophosphorylation of Ca 2+ /calmodulin-dependent protein kinase (CaMK) IIα at threonine 286 and phosphorylation of cyclic-adenosine-monophosphate response-element-binding protein (CREB) at serine 133 were markedly increased in the BLA of chronic CORT-treated mice after tone stimulation. The protein and mRNA levels of brain-derived neurotrophic factor (BDNF) also significantly increased. Our findings suggest that increased CaMKII activity and synaptic plasticity in the BLA likely account for the aberrant amygdala-dependent fear memory in chronic CORT-treated mice.
|出版物ステータス||Published - 2018 9 15|
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