title: Effect of microinjecting of 5-aza-2-deoxycytidine into ventrolateral orbital cortex on depressive-like behavior in rats.
abstract: DNA methylation and histone modification are two major epigenetic mechanisms involved in the pathophysiology of major depressive disorder (MDD) and the action of antidepressants. We and others have recently shown that epigenetic regulation through histone acetylation within ventrolateral orbital cortex (VLO) contributes to the antidepressant-like effects of histone deacetylase inhibitors [HDACi, such as valproic acid (VPA) and MS-275] observed in rats. However, there is so far no investigation focused on the effect of DNA methylation in VLO on depressive-like behaviors. Here, we examined the effects of the DNA methyltransferases (DNMTs) inhibitor 5-aza-2-deoxycytidine (5-aza) on rat forced swimming test (FST) and locomotor activity when microinjected into VLO. We found that bilateral intra-VLO injections of 5-aza increased the duration of immobility in FST in a dose-dependent manner compared to vehicle-treated controls. The effects of 5-aza observed in the FST paradigms could not be attributed to non-specific decreases in activity since the inhibition of DNA methylation in VLO did not cause general impairment in locomotor activity. These results add to the evidence that DNA hypomethylation in VLO is involved in regulating depressive-like behaviors, and suggest that the effect of DNA methylation on depressive-like behaviors appear to be brain region-dependent.
authors.affiliation: Department of Forensic Science, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, PR China; Xi'an Mental Health Center, Xi'an, Shaanxi, PR China.
authors.forename: Bo
authors.initials: B
authors.lastname: Xing
authors.affiliation: Department of Forensic Science, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, PR China; Key Laboratory of Environment and Genes Related to Diseases of Ministry of Education, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, PR China.
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.affiliation: Department of physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, PR China.
authors.forename: Wen-Jin
authors.initials: WJ
authors.lastname: Xu
authors.affiliation: Department of physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, PR China.
authors.forename: Feng-Yi
authors.initials: FY
authors.lastname: Xu
authors.affiliation: Department of Forensic Science, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, PR China; Key Laboratory of Environment and Genes Related to Diseases of Ministry of Education, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, PR China. Electronic address: psydyh@mail.xjtu.edu.cn.
authors.forename: Yong-Hui
authors.initials: YH
authors.lastname: Dang
mesh_terms: D000818:Animals; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors*; D000077209:Decitabine; D003863:Depression / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology*; D008297:Male; D008845:Microinjections; D009043:Motor Activity / Q000187:drug effects; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D017207:Rats, Sprague-Dawley
chemical_list: D000077209:Decitabine; D015254:DNA Modification Methylases; D001374:Azacitidine
keywords: DNA methylation; Depression; Forced swimming test; Ventrolateral orbital cortex