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Abstract

Targeting Mitochondrial Biogenesis in Rat Brain for Treatment of Depression

Objectives: To evaluate brain mitochondrial role in depression pathogenesis through mitochondrial Dynamin- Related Protein (Drp-1), Fission 1 Protein (Fis-1), Brain Derived Neurotrophic Factor (BDNF) and Tyrosine Kinase B (Trk-B) receptor stimulation using three different antidepressants.

Methods: Sixty four healthy adult male Sprague-Dawley rats weighing 180 ± 20 gm, were used. We established an animal model of stress-induced depressive behavior named learned helplessness (LH). LH rats were treated with fluoxetine FLX (20 mg/kg), imipramine IMP (20 mg/kg) or citalopram CTL (20 mg/kg), i.p. for 2 weeks.

Key findings: Order of decreasing number of LH rats was CTL>IMP>FLX. Brain mitochondrial SDH, MDH, IDH, MAO and SOD enzymes, Total Antioxidant Status (TAS), percentage ATP production, BDNF, Drp-1, Trk-B and Fis-1 proteins of depressed (DEP) rats significantly declined. Brain lipid peroxides were highly elevated in DEP-rats. All these levels were back to normalcy after intake of antidepressants and protein expression of BDNF, Drp-1, Trk-B, and Fis-1 were enhanced. Direct positive correlations were recorded between TAS and neurotrophins proteins among DEP-rats.

Conclusion: The use of FLX, IMP, and CTL alleviated depression induced in rats via antioxidant mechanism and neurotrophins expression modulation in rat brain mitochondria.


Author(s):

Hesham A El-Beshbishy, Hesham M El-Refaey, Hasan S Al-Amry, Rabab A Ali, Mohammed A Hassanien and Ramadan A Saad



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