Faculty of Basic Medical Sciences, Department of Physiology, Neurophysiology Unit, PAMO University of Medical Sciences, Port-Harcourt, River State, Nigeria.
Faculty of Basic Medical Sciences, Department of Physiology, Bayelsa Medical University, Yenagoa, Bayelsa State, Nigeria.
Neurochem Res. 2022 Aug;47(8):2211-2229. doi: 10.1007/s11064-022-03600-5. Epub 2022 May 9.
Activation of nuclear factor erythroid 2 related factor 2 (Nrf2) associated with the suppression of various oxido-inflammatory pathways and the controller of several gene expressions involving "antioxidant response elements" (AREs) in their promoters to mediate and restores homeostatic functions is now considered as one of the main switch regulating the immune response, and it is also now involved in inflammatory cascade in PD. Whether therapeutic approach using Ginkgo biloba would have significant protective effects against cortico-cerebellar dopaminergic degeneration in rotenone-induced mice remains unknown. In this present study, we studied the therapeutic effects of Ginkgo biloba-supplement (Gb-S) administration in cortico-cerebellar dopaminergic degeneration. The results revealed that treatment with Gb-S suppresses cognitive decline and neuromuscular incompetence in the mice, abated tyrosine hydroxylase depletion and synucleinopathy development in the cortico-cerebellar neurons of the mice before and after rotenone induction. However, our data further shows increase Nrf2 immunoexpression with decrease oxido-nitrergic and neuroinflammatory release, increase cholinergic enzyme activity and downregulated executioner caspase-3 that may mediate cortico-cerebellar apoptosis. Also, the loss of cortico-cerebellar neurons was attenuated, marked by increase in dendritic spine length and width with numerous viable neurons. Overall findings suggest that Gb-S could be a potential pharmacotherapeutic candidate providing a strong protection for cortico-cerebellar neurocellular substances and against Parkinsonism-like non-motor and motor symptoms.
核因子红细胞 2 相关因子 2（Nrf2）的激活与抑制各种氧化炎症途径有关，它还可以控制启动子中涉及“抗氧化反应元件”（AREs）的多种基因表达，从而介导和恢复体内平衡功能。目前，Nrf2 被认为是调节免疫反应的主要开关之一，它也参与了 PD 中的炎症级联反应。使用银杏叶治疗是否对鱼藤酮诱导的小鼠皮质-小脑多巴胺能变性具有显著的保护作用尚不清楚。在本研究中，我们研究了银杏叶补充剂（Gb-S）给药对皮质-小脑多巴胺能变性的治疗作用。结果表明，Gb-S 治疗可抑制小鼠的认知能力下降和神经肌肉无力，减轻鱼藤酮诱导前后皮质-小脑神经元中酪氨酸羟化酶的耗竭和突触核蛋白病的发展。然而，我们的数据进一步表明，Nrf2 免疫表达增加，氧化氮和神经炎症释放减少，胆碱能酶活性增加，执行 caspase-3 下调，这可能介导皮质-小脑细胞凋亡。此外，皮质-小脑神经元的丢失也得到了缓解，表现为树突棘长度和宽度增加，存活神经元数量增多。综上所述，Gb-S 可能是一种有潜力的药物治疗候选物，为皮质-小脑神经细胞物质提供强有力的保护，防止类似帕金森病的非运动和运动症状。
