Neuroprotective mechanism of trans,trans-Farnesol in an ICV-STZ-induced rat model of Alzheimer's pathology

被引:5
作者
Kadian, Monika [1 ]
Saini, Neetu [1 ]
Khera, Alka [2 ]
Kumar, Anil [1 ]
机构
[1] Panjab Univ, Univ Inst Pharmaceut Sci, UGC Ctr Adv Study UGC CAS, Pharmacol Div, Chandigarh 160014, India
[2] Postgrad Inst Med Educ & Res, Chandigarh 160012, India
关键词
Alzheimer's disease; Antioxidants; Memory; Reactive oxygen species; Streptozotocin; Trans; trans-Farnesol; OXIDATIVE STRESS; COGNITIVE IMPAIRMENT; MEMORY IMPAIRMENT; MITOCHONDRIAL-FUNCTION; RECOGNITION MEMORY; LIPOIC ACID; A-BETA; STREPTOZOTOCIN; DISEASE; BRAIN;
D O I
10.1007/s10787-023-01413-8
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
BackgroundAlzheimer's disease (AD) is a prominent cause of dementia, resulting in neurodegeneration and memory impairment. This condition imposes a considerable public health burden on both patients and their families due to the patients' functional impairments as well as the psychological and financial constraints. It has been well demonstrated that its aetiology involves proteinopathy, mitochondriopathies, and enhanced reactive oxygen species (ROS) generation, which are some of the key features of AD brains that further result in oxidative stress, excitotoxicity, autophagy, and mitochondrial dysfunction.ObjectiveThe current investigation was created with the aim of elucidating the neurological defence mechanism of trans,trans-Farnesol (TF) against intracerebroventricular-streptozotocin (ICV-STZ)-induced Alzheimer-like symptoms and related pathologies in rodents.Materials and methodsThe current investigation involved male SD rats receiving TF (25-100 mg/kg, per oral) consecutively for 21 days in ICV-STZ-treated animals. An in silico study was carried out to explore the possible interaction between TF and NADH dehydrogenase and succinate dehydrogenase. Further, various behavioural (Morris water maze and novel object recognition test), biochemical (oxidants and anti-oxidant markers), activities of mitochondrial enzyme complexes and acetylcholinesterase (AChE), pro-inflammatory (tumor necrosis factor-alpha; TNF-alpha) levels, and histopathological studies were evaluated in specific brain regions.ResultsRats administered ICV-STZ followed by treatment with TF (25, 50, and 100 mg/kg) for 21 days had significantly better mental performance (reduced escape latency to access platform, extended time spent in target quadrant, and improved differential index) in the Morris water maze test and new object recognition test models when compared to control (ICV-STZ)-treated groups. Further, TF treatment significantly restored redox proportion, anti-oxidant levels, regained mitochondrial capacities, attenuated altered AChE action, levels of TNF-alpha, and histopathological alterations in certain brain regions in comparison with control. In in silico analysis, TF caused greater interaction with NADH dehydrogenase and succinate dehydrogenase.ConclusionThe current work demonstrates the neuroprotective ability of TF in an experimental model with AD-like pathologies. The study further suggests that the neuroprotective impacts of TF may be related to its effects on TNF-alpha levels, oxidative stress pathways, and mitochondrial complex capabilities.
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收藏
页码:1545 / 1573
页数:29
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