title: Molecular mechanisms associated with the antidepressant effects of the class I histone deacetylase inhibitor MS-275 in the rat ventrolateral orbital cortex.
abstract: Histone modifications mediated by histone acetylation are thought to play an important role in the pathogenesis and treatment of depression. Recent studies have revealed that histone deacetylase inhibitors (HDACis), such as sodium valproate (VPA) and MS-275, may be involved in the pathogenesis of depression and in the underpinnings of antidepressant therapeutic action in several brain regions, including the ventrolateral orbital cortex (VLO). In the present study, we investigated whether the class I histone deacetylase inhibitor MS-275 exerts antidepressant-like effects when infused bilaterally into the VLO of a rat, using the forced swimming test (FST) and tail suspension test (TST) as behavioral measures. We found that chronic intra-VLO infusion of MS-275 significantly reduced immobility time in the FST and TST compared with vehicle-treated controls, similar to the effects of systemically administered fluoxetine. These antidepressant-like effects of MS-275 are associated with an increase in H3 acetylation and elevated CREB and BDNF levels in the VLO. Our findings suggest the possibility that alterations in gene expression due to chromatin remodeling, including upregulation of CREB and BDNF, may be involved in the antidepressant-like effect of HDACis in the VLO.
authors.affiliation: Department of Psychiatry, Xi'an Mental Health Center, No. 15 Yanyin Road, Xi'an, Shannxi, China. huali_lin7202@126.com
authors.forename: Huali
authors.initials: H
authors.lastname: Lin
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Geng
authors.forename: Wei
authors.initials: W
authors.lastname: Dang
authors.forename: Bin
authors.initials: B
authors.lastname: Wu
authors.forename: Zunxiao
authors.initials: Z
authors.lastname: Dai
authors.forename: Yongchun
authors.initials: Y
authors.lastname: Li
authors.forename: Yani
authors.initials: Y
authors.lastname: Yang
authors.forename: Haiyan
authors.initials: H
authors.lastname: Zhang
authors.forename: Jianguo
authors.initials: J
authors.lastname: Shi
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage*; D001549:Benzamides / Q000008:administration & dosage*; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis; D050882:CREB-Binding Protein / Q000096:biosynthesis; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology; D003863:Depression / Q000188:drug therapy* / Q000201:enzymology*; D056572:Histone Deacetylase Inhibitors / Q000008:administration & dosage*; D006655:Histone Deacetylases / Q000378:metabolism*; D008297:Male; D008845:Microinjections; D011725:Pyridines / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000928:Antidepressive Agents; D001549:Benzamides; D019208:Brain-Derived Neurotrophic Factor; D056572:Histone Deacetylase Inhibitors; D011725:Pyridines; C118739:entinostat; D050882:CREB-Binding Protein; C494365:Crebbp protein, rat; D006655:Histone Deacetylases