Neem Leaf Supplement Ameliorates Depressive Like Behaviour in Alzheimer’s Disease Model in Adult Male Wistar Rats

A. Memudu, FATIMA AYINDA Anzaku, Grace Mchibuma Jibaniya, R. Adanike
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Abstract

Aim of the Study: Currently, reports linked neuropathological changes in Alzheimer’s Disease (AD) to be a risk factor in depression. There is a need to develop natural therapeutics, with strong antioxidant property like Neem leaf, to avert AD’s neuropathological and behavioural changes using animal model induced by neurotoxin aluminium chloride. This study is aimed at ascertaining depressive like disorders in AD model while evaluating mechanism through which Neem averts AD neurodegeneration in the fronto-cerebellar cortex and possible depressive like behaviour. Methodology: Twenty (20) adult male Wistar rats used were grouped (n=5) viz: control group (A), neurodegenerative model given aluminium (B), 200mg/kg Neem leaf supplement (C) and 200mg/kg Neem leaf treated AD model (D). Neurobehavioural changes for reward memory and depressive like behaviour were evaluated using Y-maze (open arm reward test) and the tail suspension test (TST).  The frontal and cerebellar cortices were excised, fixed and processed for  Haematoxylin and Eosin stain (H and E), Cresyl fast violet (CFV) stain for Nissl bodies and astrocytes immunohistochemistry using glial fibrillary acidic protein (GFAP). Behavioural test data were analyzed using ANOVA and test for significance done @ p<0.05. Results: Aluminum induced neurodegeneration similar to AD pathology characterized by loss of neurons, chromatolysis, proliferation of astrocytes and decline in cognitive function in addition to exhibiting depressive like behaviour seen in a decrease number of reward arm entries, increase in time spent to reach reward arm and immobility time in the TST attributed to loss of cognitive function relative to loss of neurons integrity in the fronto-cerebellar cortex. However, neem leaf supplementation mitigates against AD model neuropathological and neurobehavioural  presentations resulting in an improved neurocognition, neuron survival or repair, decline in astrocytes proliferation and decline in depressive like behavior as compared to Aluminum induced AD model. Conclusion: Neem leaf alleviates depressive like behaviour associated with neurocognitive impairment through the interaction between neuron-astrocytes to protect neurons against aluminum induced neuroinflamamation and strengthens neural circuit for cognitive function.
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印度楝树叶补充剂可改善成年雄性 Wistar 大鼠阿尔茨海默氏症模型中的抑郁行为
研究目的目前,有报告称阿尔茨海默病(AD)的神经病理学变化是抑郁症的一个风险因素。有必要开发像印楝叶这样具有强抗氧化性的天然疗法,利用神经毒素氯化铝诱导的动物模型来避免阿尔茨海默病的神经病理和行为变化。本研究旨在确定 AD 模型中类似抑郁症的障碍,同时评估印楝叶避免 AD 前小脑皮层神经变性和可能的类似抑郁症行为的机制:将 20 只成年雄性 Wistar 大鼠分组(n=5),即:对照组(A)、给予铝的神经退行性模型(B)、200 毫克/千克印楝叶补充剂(C)和 200 毫克/千克印楝叶处理的 AD 模型(D)。使用 Y-迷宫(开臂奖赏试验)和尾悬试验(TST)评估奖赏记忆和抑郁样行为的神经行为变化。 对额叶和小脑皮层进行切除、固定和处理,以进行血苏木精和伊红染色(H 和 E)、甲酚快速紫(CFV)染色以检测尼氏体,并使用神经胶质纤维酸性蛋白(GFAP)对星形胶质细胞进行免疫组化。行为测试数据采用方差分析和显著性检验(P<0.05):铝诱导的神经退行性病变与注意力缺失症的病理特征相似,表现为神经元缺失、色素溶解、星形胶质细胞增殖和认知功能下降,此外还表现出类似抑郁症的行为,表现为进入奖赏臂的次数减少、到达奖赏臂所花费的时间增加以及在 TST 中不能移动的时间增加,这归因于认知功能的丧失与小脑前皮层神经元完整性的丧失有关。然而,与铝诱导的 AD 模型相比,楝树叶补充剂减轻了 AD 模型的神经病理学和神经行为表现,从而改善了神经认知、神经元存活或修复、星形胶质细胞增殖下降和抑郁样行为下降:楝树叶通过神经元-星形胶质细胞之间的相互作用,保护神经元免受铝诱导的神经损伤,并增强神经回路的认知功能,从而减轻与神经认知障碍相关的抑郁行为。
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