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The behavioral deficits and cognitive impairment are correlated with decreased IGF-II and ERK in depressed mice induced by chronic unpredictable stress

ABSTRACT Aim: To investigate the behavioral deficits, cognitive impairment and possible mechanisms induced by chronic unpredictable stress (CUS) in mice of different ages. Methods: The behaviors and cognition were tested using the open field test, tail suspension test and the Morris water maze. The changes in the insulin-like growth factor II (IGF-II) and the extracellular signal-regulated kinase (ERK) and phosphorylation (p-ERK) in the hippocampus (HP) and prefrontal cortex (PFC) were evaluated by immunohistochemistry. Results: The 15-month-old mice revealed a significant decline in spontaneous behavior and the learning–memory function and showed a decrease in IGF-II and p-ERK expression levels in HP and PFC. Four weeks of CUS exposure induced significant anxiety- and depression-like behavior and learning–memory function impairment in 3- to 15-month-old mice, and reduced IGF-II and p-ERK expression levels in HP and PFC, compared with control group mice, respectively. Conclusions: The behavioral deficits and cognitive impairment induced by CUS and aging in mice could be associated with the down-regulated expression of IGF-II and p-ERK in HP and PFC. This role seems to be dependent on the intracellular ERK pathway.