Iranian Biomedical Journal

en Antidepressant Effects of L-Arginine and Its Role in Brain Energy Metabolism Tissue Engineering and Cell Biology Tissue Engineering and Cell Biology مقاله کامل Full Length/Original Article <div style="text-align: justify;">Background: Mitochondrial dysfunction and impaired cellular energy metabolism are increasingly recognized as key contributing factors in depression. This study evaluated the amino acid L-arginine as a potential agent for behavioral rescue and bioenergetic restoration using a corticosterone-induced rat model of depression. Methods: Male rats were randomly assigned to four groups (n = 10): control (DMSO intraperitoneally [i.p.] + water oral gavage), corticosterone-induced depression (20 mg/kg, i.p. for 14 days), L-arginine treatment (150 mg/kg, oral gavage for 14 days), and fluoxetine (10 mg/kg, oral gavage for 14 days). To ensure handling equivalence, all oral administrations were performed via gavage (1.0 mL/100 g). Behavioral rescue was assessed via open field, forced swim (FST), and tail suspension (TST) tests. Hippocampal energy metabolism and PI3K/Akt/mTOR pathway activation were analyzed. Results:  L-arginine significantly improved the hippocampal bioenergetic profile, demonstrating efficacy comparable to the positive control fluoxetine. It led to a significant reduction in immobility time during FST and TST, alongside restoring glycolysis, the tricarboxylic acid cycle, and mitochondrial respiratory chain activities. Concurrently, L-arginine enhanced the activation state of the PI3K/Akt/mTOR signaling pathway (phosphorylated Akt/Akt and p-mTOR/mTOR ratios) and improved the functional state of the mitochondrial permeability transition pore. These metabolic and signaling improvements strongly correlated with the rescue of depressive-like behaviors. Conclusion: Our findings demonstrate that L-arginine possesses potent antidepressant-like potential, mediated through bioenergetic restoration and signaling pathway modulation. By activating key metabolic processes in the hippocampus, L-arginine effectively restores impaired cellular energy homeostasis, suggesting its promise as a metabolic modulator for alleviating neurobiological disturbances associated with depressive conditions. </div> Arginine, Corticosterone, Depression, Energy metabolism, Hippocampus 141 152 http://ibj.pasteur.ac.ir/browse.php?a_code=A-10-6570-1&slc_lang=en&sid=1 Temuri Mantashashvili Temuri.Mantashashvili6037@ens.tsu.edu.ge 0000-0002-9738-1027 Yes Department of Biology, Ivane Javakhishvili Tbilisi State University, 11th Building, University Street, 0186, Tbilisi, Georgia Luka Nakaidze lukanakaidze08@gmail.com 0009-0004-9396-397X No Department of Biology, Ivane Javakhishvili Tbilisi State University, 11th Building, University Street, 0186, Tbilisi, Georgia Mariam Shengelia mariam.shengelia@tsu.ge 0009-0001-1276-5030 No Department of Biology, Ivane Javakhishvili Tbilisi State University, 11th Building, University Street, 0186, Tbilisi, Georgia Nana Koshoridze nana.koshoridze@tsu.ge 0000-0002-6856-174X No Department of Biology, Ivane Javakhishvili Tbilisi State University, 11th Building, University Street, 0186, Tbilisi, Georgia