title: Disrupted MEK/ERK signaling in the medial orbital cortex and dorsal endopiriform nuclei of the prefrontal cortex in a chronic restraint stress mouse model of depression.
abstract: Depression is one of the most prevalent mental illnesses, and causes a constant feeling of sadness and lose of interest, which often leads to suicide. Evidence suggests that depression is associated with aberrant MEK/ERK signaling. However, studies on MEK/ERK signaling in depression have only been done in a few brain regions, such as the hippocampus and mesolimbic reward pathways. Recent studies also implicate the involvement of the prefrontal cortex in depression. Thus, we examined the changes in MEK/ERK signaling in subregions of the prefrontal cortex of C57BL/6 mice by immunohistochemistry using phospho-MEK1/2 (Ser 217/221) and ERK1/2 (Thr202/Tyr204) antibodies. Mice were subjected to 21 consecutive days of restraint stress (for 2h daily), and depression-like behavior was evaluated using a sociability test and tail suspension test. The antidepressant, imipramine (20mg/kg) was injected intraperitoneally 30min before restraint stress exposure. Chronic/repeated restraint stress produced depressive-like behavior, such as increased social avoidance in the social interaction test, and enhanced immobility time in the tail suspension test. This depressive behavior was ameliorated by imipramine. The behavioral changes well corresponded to a decrease in MEK/ERK immunoreactivity in the medial orbital (MO) cortex and dorsal endopiriform nuclei (DEn), which was averted by imipramine, but not in cingulate, prelimbic, infralimbic, and motor cortex. These results suggest that MEK/ERK signaling is disrupted in the DEn and MO subregions of the prefrontal cortex in the depressive phenotype, and that blocking a decrease in activated MEK/ERK is inherent to the antidepressant imipramine response.
authors.affiliation: Department of Pharmacy, College of Pharmacy, Dankook University, Cheonan-si, Chungnam 330-951, Republic of Korea.
authors.forename: Yea-Hyun
authors.initials: YH
authors.lastname: Leem
authors.affiliation: Department of Nanobiomedical Science & BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan-si, Chungnam 330-951, Republic of Korea.
authors.forename: Sang-Sun
authors.initials: SS
authors.lastname: Yoon
authors.affiliation: Department of Nanobiomedical Science & BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan-si, Chungnam 330-951, Republic of Korea.
authors.forename: Yu-Han
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Department of Pharmacy, College of Pharmacy, Dankook University, Cheonan-si, Chungnam 330-951, Republic of Korea; Department of Nanobiomedical Science & BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan-si, Chungnam 330-951, Republic of Korea. Electronic address: smahn@dankook.ac.kr.
authors.forename: Sangmee Ahn
authors.initials: SA
authors.lastname: Jo
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use; D002908:Chronic Disease; D003863:Depression / Q000201:enzymology* / Q000523:psychology; D007099:Imipramine / Q000627:therapeutic use; D008297:Male; D008810:Mice, Inbred C57BL; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D010766:Phosphorylation; D066195:Piriform Cortex / Q000201:enzymology*; D017397:Prefrontal Cortex / Q000201:enzymology*; D012149:Restraint, Physical; D013315:Stress, Psychological / Q000188:drug therapy / Q000201:enzymology* / Q000523:psychology
chemical_list: D000928:Antidepressive Agents; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D007099:Imipramine
keywords: Dorsal endopiriform nuclei; ERK; MEK; Medial orbital cortex; Restraint stress; Social interaction