title: Antidepressant-like effect of n-3 PUFAs in CUMS rats: role of tPA/PAI-1 system.
abstract: BDNF is strongly implicated in the development of depression. Recent evidence has indicated that tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) are related to the cleavage of pro-brain-derived neurotrophic factor (BDNF) into its mature form. Chronic unpredicted mild stress (CUMS) is widely used to induce depressive behaviors in rodents. Therefore, we investigated the effects of PUFAs and sertraline on tPA/PAI-1 system in CUMS rats. After 5 weeks of CUMS procedures, the rats were induced to a depressive-like state. The expressions of PAI-1 and proBDNF were increased in the prefrontal cortex and hippocampus of CUMS rats. N-3 polyunsaturated fatty acids (PUFAs) or sertraline administration reversed the changes in behavioral test and induced the expression of tPA in certain brain areas, but failed to restore the CUMS-induced PAI-1 expression. Meanwhile, the antidepressant treatment also accelerated the extracellular conversion of proBDNF into mature BDNF in CUMS rats. Our results firstly showed the synchronously altered balance of tPA/PAI-1 system in the prefrontal cortex and hippocampus of CUMS rats, which was partly ameliorated by PUFAs and sertraline medication, providing new evidence for the involvement of tPA/PAI-1 system in the progression and treatment of depression.
authors.affiliation: Institute of Clinical Pharmacy & Pharmacology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China; School of Pharmaceutical Sciences, Central South University, Changsha, China.
authors.forename: Mimi
authors.initials: M
authors.lastname: Tang
authors.affiliation: Institute of Clinical Pharmacy & Pharmacology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China; School of Pharmaceutical Sciences, Central South University, Changsha, China.
authors.forename: Pei
authors.initials: P
authors.lastname: Jiang
authors.affiliation: Institute of Clinical Pharmacy & Pharmacology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China. Electronic address: lihuande1953@126.com.
authors.forename: Huande
authors.initials: H
authors.lastname: Li
authors.affiliation: Institute of Clinical Pharmacy & Pharmacology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Hualin
authors.initials: H
authors.lastname: Cai
authors.affiliation: Institute of Clinical Pharmacy & Pharmacology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Yiping
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Institute of Clinical Pharmacy & Pharmacology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Gong
authors.affiliation: Institute of Clinical Pharmacy & Pharmacology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China; School of Pharmaceutical Sciences, Central South University, Changsha, China.
authors.forename: Lihong
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001835:Body Weight; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002908:Chronic Disease; D003866:Depressive Disorder / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000503:physiopathology; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D020280:Sertraline / Q000494:pharmacology*; D013315:Stress, Psychological / Q000503:physiopathology; D010959:Tissue Plasminogen Activator / Q000378:metabolism*
chemical_list: D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D015525:Fatty Acids, Omega-3; D017395:Plasminogen Activator Inhibitor 1; D010959:Tissue Plasminogen Activator; D020280:Sertraline
keywords: Brain-derived neurotrophic factor; Chronic unpredicted mild stress; Plasminogen activator inhibitor-1; Polyunsaturated fatty acids; Sertraline; Tissue plasminogen activator