Alzheimer’s disease (AD) accounts for 80% of all dementia cases, making it the most common form of dementia. Aging serves as the main risk factor for AD, but early onset AD can also occur in individuals younger than 65 years. AD results from progressive neurodegeneration leading to dysfunctional synaptic transmission in the brain. The cascade hypothesis of AD states that amyloid precursor protein (APP) metabolism becomes impaired either by mutation or an interleukin-mediated stress response to injury, resulting in the splicing of harmful oligomeric forms of amyloid beta (Aβ). These oligomers disrupt extracellular receptor binding, intracellular function, and cellular membrane integrity. Yoga and meditative practices slow the progression of the cognitive decline associated with AD. However, the biological mechanisms underlying this therapeutic effect remain elusive. Here, we investigated the ability of neurotransmitters released during yoga and meditative practices to rescue neurons from synaptic dysfunction in an in vitro Alzheimer’s model created by culturing basal forebrain cholinergic neurons with physiologically relevant levels of the I-42 isoform of oligomeric Aβ (OΑβI-42). We found that the neurotransmitters dopamine and histamine produce a cooperative action with serotonin to reverse the loss of choline acetyltransferase (CHaT) by OΑβI-42. The loss of ChaT, the enzyme responsible for processing the cholinergic neurotransmitter acetylcholine, contributes to the synaptic dysfunction experienced during AD. These neurotransmitters inhibit nitric oxide synthesis caused by OΑβI-42, preventing oxidative and nitrosative stress. Serotonin activates an alternate cleavage of APP to produce a fragment with known neurotrophic effects, giving it the unique ability to inhibit the OΑβI-42 production cycle. We hypothesize here that these concerted actions lead to the protection of cholinergic synaptic transmission in AD.

中文翻译：

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模拟瑜伽对盘中阿尔茨海默病进展的影响

阿尔茨海默病 (AD) 占所有痴呆症病例的 80%，使其成为最常见的痴呆症形式。衰老是 AD 的主要危险因素，但早发性 AD 也可能发生在 65 岁以下的个体中。AD 是由进行性神经变性导致大脑中突触传递功能障碍引起的。AD 的级联假设指出，淀粉样前体蛋白 (APP) 的代谢因突变或白介素介导的损伤应激反应而受损，导致有害的淀粉样蛋白 β (Aβ) 寡聚形式的剪接。这些寡聚体破坏细胞外受体结合、细胞内功能和细胞膜完整性。瑜伽和冥想练习减缓了与 AD 相关的认知能力下降的进程。然而，这种治疗效果背后的生物学机制仍然难以捉摸。在这里，我们研究了瑜伽和冥想练习期间释放的神经递质在体外阿尔茨海默病模型中从突触功能障碍中拯救神经元的能力，该模型是通过培养具有生理相关水平的寡聚 Aβ (OAβI-42) 的 I-42 异构体的基底前脑胆碱能神经元而创建的。 ）。我们发现神经递质多巴胺和组胺与血清素产生协同作用以逆转 OAβI-42 对胆碱乙酰转移酶 (CHaT) 的损失。ChaT（负责处理胆碱能神经递质乙酰胆碱的酶）的缺失导致 AD 期间经历的突触功能障碍。这些神经递质抑制由 OAβI-42 引起的一氧化氮合成，防止氧化和亚硝化应激。血清素激活 APP 的交替裂解以产生具有已知神经营养作用的片段，使其具有抑制 OAβI-42 生产周期的独特能力。我们在此假设这些协同作用会保护 AD 中的胆碱能突触传递。