Dysregulation of Neuregulin-1/ErbB signaling in the prefrontal cortex and hippocampus of rats exposed to chronic unpredictable mild stress.

ABSTRACT

Exposure to chronic stress increases the likelihood of developing depression, but the underlying mechanisms remain equivocal. While recent evidence has indicated that Neuregulin-1 (NRG1) and its ErbB receptors play an essential role in neural development and function, and NRG1 has emerged as a novel modulator involved in the response of brain to stress, there is limited evidence concerning the effects of chronic stress exposure on NRG1/ErbB signaling. To fill this critical gap, we examined the protein expression of NRG1 and ErbB receptors in the brain of rats following chronic unpredictable mild stress (CUMS) exposure. After 6weeks of CUMS procedures, the rats were induced to a depression-like state. The stressed rats displayed elevated expression of NRG1 and phosphorylated ErbB4 (pErbB4) in the prefrontal cortex, whereas ErbB2 and pErbB2 were inhibited. In the hippocampus, CUMS also attenuated activation of the both ErbB receptors and suppressed the downstream Akt and ERK phosphorylation. Meanwhile, administration of sertraline enhanced NRG1/ErbB signaling and partly normalized the stress-induced behavioral changes and the disturbances of NRG1/ErbB system in CUMS rats. Combined, our data firstly showed the aberrant changes of NRG1/ErbB system in the brain of the animal model of depression, providing new evidence for the involvement of NRG1/ErbB pathway in the development and treatment of depression.