Olanrewaju John Afees, Owolabi Joshua Oladele, Awodein Ifedamola Patience, Enya Joseph Igbo, Adelodun Stephen Taiye, Olatunji Sunday Yinka, Fabiyi Sunday Oluwaseyi
Department of Anatomy, Ben Carson School of Medicine, Babcock University, Ilishan-Remo, Ogun State, Nigeria.
Department of Anatomy, Faculty of Basic Medical Sciences, University of Ilorin, Ilorin, Nigeria.
J Exp Pharmacol. 2020 Nov 2;12:439-446. doi: 10.2147/JEP.S275260. eCollection 2020.
Repeated and regimented treatment with reserpine causes depression-like condition characterized by persistent mood disorder, feelings of severe despondency and dejection, thus altering the hippocampal morphology. Our study compared a well-known antidepressant (fluoxetine), with the potential of to ameliorate reserpine-induced depression and the associated hippocampal cornu ammonis 1 (CA1) neuronal cell damage.
Forty-eight male Wistar rats, weighing 130-160 g, were randomly assigned to 6 groups (n=8), housed in plastic cages under natural light and dark cycles at room temperature with access to feed and water . Group-A (control) received distilled water. Group-B and Group-C orally received 400 mg/kg of and 10 mg/kg of fluoxetine, respectively, for 7 days, while Group-D intraperitoneally received 0.2 mg/kg of reserpine for 14 days. Group-E and Group-F intraperitoneally received 0.2 mg/kg of reserpine for 14 days followed by 400 mg/kg of and 10 mg/kg of fluoxetine respectively for 7 days. All animals were sacrificed by cervical dislocation at the end of experiment, and the brains hippocampi were dissected, excised and processed for various analyses including histology [H&E], histochemistry of GFAP expression by astrocytes and specific gene expressions including p53 gene, glutathione reductase (GSR), glutathione peroxidase and catalase (CAT).
Reserpine significantly depleted the expression of P53 and glutathione reductase (GSR) genes while significantly increasing the expression of glutathione peroxidase 1 (GPx-1) gene (P≤0.05). Also, a marked increase in the expression of catalase (CAT) gene was observed. Furthermore, histoarchitecture (photomicrographs) of hippocampus CA1 region showed disruption in the arrangement of pyramidal neurons and alterations in their morphologies when animals were treated with reserpine (Group D). There was also accompanying increased astrocyte densities within the CA1 region following reserpine treatment. These features indicated deleterious effects of reserpine. Both and fluoxetine treatments ameliorated these effects.
These findings showed structural and molecular alterations associated with reserpine-induced depression. Also, was effective to provide ameliorative and protective effects against the neurotoxic effects of reserpine in the hippocampus, making it a potential candidate for treating depression and its associated neurodegenerative diseases.
反复且规律地使用利血平治疗会导致类似抑郁的状态，其特征为持续的情绪障碍、严重的沮丧和抑郁情绪，从而改变海马体形态。我们的研究比较了一种知名的抗抑郁药（氟西汀）改善利血平诱导的抑郁及相关海马体1区（CA1）神经元细胞损伤的潜力。
48只体重130 - 160克的雄性Wistar大鼠被随机分为6组（每组n = 8），饲养在塑料笼中，处于自然光照和黑暗周期下，室温环境，可自由获取食物和水。A组（对照组）给予蒸馏水。B组和C组分别口服400毫克/千克的[物质名称缺失]和10毫克/千克的氟西汀，持续7天，而D组腹腔注射0.2毫克/千克的利血平，持续14天。E组和F组腹腔注射0.2毫克/千克的利血平，持续14天，随后分别口服400毫克/千克的[物质名称缺失]和10毫克/千克的氟西汀，持续7天。实验结束时，所有动物通过颈椎脱臼法处死，解剖大脑海马体，切除并进行各种分析，包括组织学[苏木精-伊红染色（H&E）]、星形胶质细胞GFAP表达的组织化学以及特定基因表达，包括p53基因、谷胱甘肽还原酶（GSR）、谷胱甘肽过氧化物酶和过氧化氢酶（CAT）。
利血平显著降低了P53和谷胱甘肽还原酶（GSR）基因的表达，同时显著增加了谷胱甘肽过氧化物酶1（GPx - 1）基因的表达（P≤0.05）。此外，还观察到过氧化氢酶（CAT）基因的表达显著增加。此外，当用利血平处理动物时（D组），海马体CA1区的组织架构（显微照片）显示锥体细胞排列紊乱，形态改变。利血平处理后，CA1区内星形胶质细胞密度也随之增加。这些特征表明利血平具有有害作用。[物质名称缺失]和氟西汀治疗均改善了这些影响。
这些发现表明了与利血平诱导的抑郁相关的结构和分子改变。此外，[物质名称缺失]对利血平在海马体中的神经毒性作用具有改善和保护作用，使其成为治疗抑郁症及其相关神经退行性疾病的潜在候选药物。
