Abstract
Chronic stress appears to alter DNA methylation and DNA methyltransferases (DNMTs) in brain regions related to emotion. Collapsin response mediator protein-2 (CRMP2) mediates the development of depression by regulating microtubule dynamics. In this study, rats were subjected to chronic unpredictable mild stress (CUMS). At the end of the CUMS procedure, normal saline or fluoxetine was administered to the rats. Moreover, normal saline or the 5-aza-2’-deoxycytidine (5-aza) was administered to the hippocampal CA1 region of the rats. Behavioral tests were performed to evaluate the depressive-like phenotypes. The CRMP2 DNA methylation levels and cytoskeletal microtubular system-related biomarkers were detected by several molecular biology techniques. The results showed that the rat model of depression was successfully established by exposure to CUMS, and fluoxetine treatment exerted an antidepressant-like effect. We observed the upregulation of DNMT1 and DNMT3a in the hippocampus of stressed rats. CUMS induced a decrease in CRMP2 expression and an increase in phosphorylated CRMP2 (pCRMP2) expression in the hippocampus of rats. The rate of DNA methylation in the CpG island of the CRMP2 promoter region in the hippocampus of stressed rats was significantly higher than that in control rats. Moreover, CUMS significantly decreased the interaction between CRMP2 and α-tubulin and decreased the microtubule dynamics. Chronic fluoxetine treatment reversed these changes. Also, hypomethylation induced by 5-aza injection into the hippocampal CA1 region caused antidepressant-like effects and increased CRMP2 expression and microtubule dynamics. These results suggested that CRMP2 DNA methylation may be involved in regulating the cytoskeletal microtubular system and mediating depressive-like behaviors.
Highlights
As a severe psychiatric disorder, depression is characterized by a depressed mood or a marked loss of interest or pleasure for most of the day
Immobility time in the FST was used to evaluate the symptom of helplessness in a rat model of depression (Paré, 1992)
The rat model of depression was successfully established by exposure to chronic unpredictable mild stress (CUMS) for 4 weeks
Summary
As a severe psychiatric disorder, depression is characterized by a depressed mood or a marked loss of interest or pleasure for most of the day. Depression is a common illness worldwide, and more than 300 million people are currently depressed. Depression has substantial adverse effects on personal health, with high recurrence and mortality. Depression is linked to cerebrovascular disease, and depressed patients are at higher risk of stroke, with an enormous. CRMP2 DNA Methylation in Depression burden for patients, families, and society as a whole (Kolovos et al, 2017; Winter et al, 2018). Various treatments are effective against depression, some patients are resistant to the currently available treatments. The underlying mechanisms that cause depression are still unclear. It is necessary to identify the mechanisms underlying depression
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