Differential Regulation of DNA Methylation at the CRMP2 Promoter Region Between the Hippocampus and Prefrontal Cortex in a CUMS Depression Model

Abstract

Current evidence supports the idea that neural plasticity is a potential cause of depression. Abundant studies indicate that CRMP2 has important roles in neural plasticity. Moreover, CRMP2 may contribute to the etiology of depression. However, the regulatory mechanisms underlying the role of CRMP2 remain unclear. DNA methylation alteration is generally acknowledged to be involved in the development of depression. The aim of this study was to explore the relationship between the expression and DNA methylation of CRMP2 in the hippocampus and prefrontal cortex of a rat depression model. Chronic unpredictable mild stress (CUMS) was used to establish a rat depression model, and body weight and behavioral tests were used to evaluate the effects of stress. Real-time PCR and Western blotting were used to test CRMP2 mRNA and protein expression, respectively, in the hippocampus and prefrontal cortex of rats. DNA methylation levels of the CRMP2 promoter were analyzed by bisulfite sequencing PCR (BSP). CUMS caused depressive-like behavior in rats, as evidenced by: decreased body weight and sucrose preference rate; decreases in the total distance traveled, rearing frequency, velocity, and duration in the center in the open field test (OFT); and prolonged immobility in the forced swimming test (FST). CRMP2 mRNA and protein expression in the hippocampus and prefrontal cortex were significantly decreased in the CUMS group compared with the control group. The levels of CRMP2 promoter DNA methylation in the hippocampus of the CUMS group were significantly higher than those of the control group, while these changes were not observed in the prefrontal cortex of CUMS rats. Our data provide evidence that altered expression of CRMP2 in the hippocampus and prefrontal cortex is associated with the pathogenesis of depression. Moreover, the results also suggest regional differences in the regulation of DNA methylation in the CRMP2 promoter between the hippocampus and prefrontal cortex during the development of depression.

Early Life Stress Induced DNA Methylation of Monoamine Oxidases Leads to Depressive-Like Behavior

“…This indicates that the changes in CRMP2 expression in the hippocampus and prefrontal cortex are related to the pathogenesis of depression. In addition, the results also show regional differences in the regulation of DNA methylation in the CRMP2 promoter between the hippocampus and the prefrontal cortex during the development of depression (Xiang et al, 2020). DNA methylation is a dynamic tissue-specific event that may play an important role in the persistent and recurrent nature of depression.…”

Effects of CRMP2 DNA Methylation in the Hippocampus on Depressive-Like Behaviors and Cytoskeletal Proteins in Rats

“…CRMP2 has been proposed to be a candidate gene for the treatment of depression. In our previous study, the results showed a reduction in CRMP2 expression in the hippocampus of stressed rats, which may correlate with a significant increase in the DNA methylation levels of the CRMP2 promoter region (Xiang et al, 2020). Moreover, several studies suggested the important role of DNMTs in regulating depressive-like behaviors (Ignácio et al, 2017;Shen et al, 2019).…”

Peripheral and central pathophysiological changes in a new rat model of acid reflux combined with mental stress

“…A video camera was configured above the field to monitor the locomotor activities of rats, including the number of square crossings, the number of rearing, and the number of grooming events within 5 min. The fewer the number of walk grids, the lesser the number of standing up, and the more the number of grooming, the more nervous the rats were 18 . The field was cleaned with alcohol for each test.…”

“…The fewer the number of walk grids, the lesser the number of standing up, and the more the number of grooming, the more nervous the rats were. 18 The field was cleaned with alcohol for each test. The final data were analyzed using a video capture master (VideoMot2, TSE Company, Germany).…”