The pro-oxidant compound okadaic acid (OKA) mimics alterations found in Alzheimer’s disease (AD) as oxidative stress and tau hyperphosphorylation, leading to neurodegeneration and cognitive decline. Although loss of dendrite complexity occurs in AD, the study of this post-synaptic domain in chemical-induced models remains unexplored. Moreover, there is a growing expectation for therapeutic adjuvants to counteract these brain dysfunctions. Melatonin, a free-radical scavenger, inhibits tau hyperphosphorylation, modulates phosphatases, and strengthens dendritic arbors. Thus, we determined if OKA alters the dendritic arbors of hilar hippocampal neurons and whether melatonin prevents, counteracts, or reverses these damages. Rat organotypic cultures were incubated with vehicle, OKA, melatonin, and combined treatments with melatonin either before, simultaneously, or after OKA. DNA breaks were assessed by TUNEL assay and nuclei were counterstained with DAPI. Additionally, MAP2 was immunostained to assess the dendritic arbor properties by the Sholl method. In hippocampal hilus, OKA increased DNA fragmentation and reduced the number of MAP2(+) cells, whereas melatonin protected against oxidation and apoptosis. Additionally, OKA decreased the dendritic arbor complexity and melatonin not only counteracted, but also prevented and reversed the dendritic arbor retraction, highlighting its role in post-synaptic domain integrity preservation against neurodegenerative events in hippocampal neurons.

中文翻译：

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褪黑激素挽救大鼠海马器官型培养中促氧化毒素冈田酸诱导的树突塌陷

促氧化化合物冈田酸 (OKA) 模拟阿尔茨海默病 (AD) 中发现的氧化应激和 tau 过度磷酸化的改变，导致神经变性和认知能力下降。尽管 AD 中发生树突复杂性的丧失，但在化学诱导模型中对这种突触后结构域的研究仍未得到探索。此外，人们越来越期望使用治疗辅助剂来抵消这些脑功能障碍。褪黑激素是一种自由基清除剂，可抑制 tau 过度磷酸化、调节磷酸酶并增强树突乔木。因此，我们确定 OKA 是否会改变海马门神经元的树突乔木，以及褪黑激素是否可以预防、抵消或逆转这些损伤。大鼠器官型培养物与媒介物、OKA、褪黑激素一起孵育，并在之前与褪黑激素联合处理，同时，或在 OKA 之后。通过 TUNEL 测定评估 DNA 断裂，并用 DAPI 复染细胞核。此外，MAP2 被免疫染色以通过 Sholl 方法评估树突乔木特性。在海马门中，OKA 增加了 DNA 片段化并减少了 MAP2(+) 细胞的数量，而褪黑激素可防止氧化和细胞凋亡。此外，OKA 降低了树突乔木的复杂性，褪黑激素不仅抵消了，而且还阻止和逆转了树突乔木回缩，突出了其在突触后结构域完整性保护中的作用，以防止海马神经元中的神经退行性事件。在海马门中，OKA 增加了 DNA 片段化并减少了 MAP2(+) 细胞的数量，而褪黑激素可防止氧化和细胞凋亡。此外，OKA 降低了树突乔木的复杂性，褪黑激素不仅抵消了，而且还阻止和逆转了树突乔木回缩，突出了其在突触后结构域完整性保护中的作用，以防止海马神经元中的神经退行性事件。在海马门中，OKA 增加了 DNA 片段化并减少了 MAP2(+) 细胞的数量，而褪黑激素可防止氧化和细胞凋亡。此外，OKA 降低了树突乔木的复杂性，褪黑激素不仅抵消了，而且还阻止和逆转了树突乔木回缩，突出了其在突触后结构域完整性保护中的作用，以防止海马神经元中的神经退行性事件。