title: Possible involvement of the JAK/STAT signaling pathway in N-acetylcysteine-mediated antidepressant-like effects.
abstract: Advances in depression research have targeted inflammation and oxidative stress to develop novel types of treatment. The JAK/STAT signaling pathway plays pivotal roles in immune and inflammatory responses. The present study was designed to investigate the effects of N-acetylcysteine, a putative precursor of the antioxidant glutathione, in an animal model of depression, with an emphasis on the JAK/STAT signaling pathway. Fluoxetine, a classical antidepressant drug was also under investigation. Male Wistar rats were subjected to forced swimming test and given N-acetylcysteine and fluoxetine immediately after the pre-test session, 5 h later and 1 h before the test session of the forced swimming test. N-acetylcysteine decreased immobility time (P < 0.05), serum corticosterone (P < 0.001), and hydrogen peroxide (P < 0.001), while restored glutathione concentration. Treatment of the rats with N-acetylcysteine produced significant (P < 0.001) down-regulation of STAT3 mRNA expression and protein phosphorylation. On the other hand, N-acetylcysteine significantly (P < 0.001) increased SOCS3 gene expression; however, SOCS3 protein was not changed. In conclusion, our study suggests that modulation of the JAK/STAT pathway might mediate the antidepressant-like effects of N-acetylcysteine. Therefore, depression research may target the JAK/STAT signaling pathway to provide a novel effective therapy.
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 12372, Saudi Arabia.
authors.forename: Marwa M
authors.initials: MM
authors.lastname: Al-Samhari
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 12372, Saudi Arabia.
authors.forename: Nouf M
authors.initials: NM
authors.lastname: Al-Rasheed
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 12372, Saudi Arabia.
authors.forename: Salim
authors.initials: S
authors.lastname: Al-Rejaie
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 12372, Saudi Arabia Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah bint Abdulrahman University, Riyadh 22452, Saudi Arabia.
authors.forename: Nawal M
authors.initials: NM
authors.lastname: Al-Rasheed
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 12372, Saudi Arabia.
authors.forename: Iman H
authors.initials: IH
authors.lastname: Hasan
authors.affiliation: Department of Physiology, College of Medicine, King Saud University, Riyadh 12372, Saudi Arabia Physiology Division, Department of Zoology, Faculty of Science, Beni-Suef University, Beni-Suef 62514, Egypt ayman.mahmoud@science.bsu.edu.eg.
authors.forename: Ayman M
authors.initials: AM
authors.lastname: Mahmoud
authors.affiliation: Department of Genetics, King Faisal Specialist Hospital & Research Centre, Riyadh 12713, Saudi Arabia.
authors.forename: Nduna
authors.initials: N
authors.lastname: Dzimiri
mesh_terms: D000111:Acetylcysteine / Q000008:administration & dosage*; D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage*; D000975:Antioxidants; D001522:Behavior, Animal; D003863:Depression / Q000188:drug therapy*; D004195:Disease Models, Animal; D005473:Fluoxetine / Q000008:administration & dosage; D053612:Janus Kinases / Q000378:metabolism*; D008297:Male; D018384:Oxidative Stress; D017208:Rats, Wistar; D050791:STAT Transcription Factors / Q000378:metabolism*; D015398:Signal Transduction; D013550:Swimming
chemical_list: D000928:Antidepressive Agents; D000975:Antioxidants; D050791:STAT Transcription Factors; D005473:Fluoxetine; D053612:Janus Kinases; D000111:Acetylcysteine
keywords: Depression; SOC3; forced swimming test; glutathione; inflammation; oxidative stress