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.

KEYWORDS:

• CUS
• behavior
• learning and memory
• IGF-II
• ERK

Disclosure statement

The authors report no conflicts of interest.

Additional information

Funding

Shandong Provincial Natural Science Foundation of China [grant number ZR2009DL009]; Excellent Young and Middle-Aged Scientists Foundation of Shandong Province, China [grant number BS2012SW021].

Notes on contributors

Ya Li

Ya Li is a professor in College of Life Sciences at Qufu Normal University. He obtained his PH.D. degree in Physiology from School of Life Sciences of Nanjing University in 2004. Currently his research interests are in the area of cellular and molecular mechanism in learning and memory, and pharmacological effects of psychotropic drugs.

Yajing Chen

Yajing Chen obtained her M.S. degree in College of Life Sciences at Qufu Normal University in 2012.

Xiaoxiao Gao

Xiaoxiao Gao is an M.S. degree candidate.

Zhongqiu Zhang

Zhongqiu Zhang is an M.S. degree candidate.