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Creatine and Alpha-lipoic Acid Antidepressant-like Effect in Mice Following CyclosporineA Administration, and The Level of BDNF
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Azadeh Mesripour   , Mehdi Aliomran , Abolfazl Saleki Mehrjardi |
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Abstract: (224 Views) |
Introduction: Cyclosporin A (CYA) is a calcineurin inhibitor that is used as an immunosuppressive drug. Psychological problems such as depression and anxiety may occur while taking cyclosporine. In this study, the antidepressant effects of creatine as a regulator of oxidative phosphorylation and alpha-lipoic acid (ALA), as a cofactor for the mitochondrial respiratory chain, were investigated following the administration of cyclosporine.
Methods and Materials: Female mice (weighing 27±2 g) were used, evaluating the locomotor activity immobility time during the forced swimming test (FST) was measured as an indicator of animal despair, and hippocampal Brain-derived neurotrophic factor (BDNF) level was evaluated. CYA (20 mg/kg) IP vehicle (2% EtOH/normal saline), creatine 10 mg/kg gavage feeding tube, and ALA 40 mg/kg IP were administered for 6 consecutive days, and the tests were performed on day 7. Fluoxetine was chosen for the control-positive group.
Results: The locomotor activity was not significantly different among the study groups. CYA increased immobility time during FST (175.1±13.16s, vs. vehicle 130.9±13.5s, p=0.0364) that indicates a depressive-like effect, and by treating the animals with ALA (100±15.9s, p=0.020) or creatine (93.5±16.6, p=0.009) as fluoxetine the immobility time significantly decreased compared to CYA. ALA and creatine co-administration showed a synergy effect on immobility time (12.2±2.59s, p<0.001 vs CYA). Unexpectedly, CYA increased BDNF level (1059±81.0 pg/mg protein, vs vehicle p= 0.0093). ALA and ALA, creatine co-administration significantly reduced BDNF levels compared with CYA, creatine alone did not change the result.
Conclusion: CYA-induced depressive-like effect is partly related to mitochondrial dysfunction and neurotoxicity since it was prevented by mitochondrial antioxidant ALA and creatine. On the other hand, the BDNF level increased following CYA administration, and AIA similar to fluoxetine prevented this effect. |
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| Keywords: Cyclosporine, depression, creatine, alpha-lipoic acid, brain-derived neurotrophic factor |
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Full-Text [PDF 395 kb]
(27 Downloads)
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Type of Study: Research |
Subject:
General
Received: 2024/02/10 | Accepted: 2023/08/23 | Published: 2023/08/23
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