Department of Morphology and Cell Biology, University of Oviedo, 33006 Oviedo, Asturias, Spain.
Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Asturias, Spain.
Molecules. 2022 Aug 29;27(17):5543. doi: 10.3390/molecules27175543.
Adult hippocampal neurogenesis is altered during aging and under different neuropsychiatric and neurodegenerative diseases. Melatonin shows neurogenic and neuroprotective properties during aging and neuropathological conditions. In this study, we evaluated the effects of chronic treatment with melatonin on different markers of neurodegeneration and hippocampal neurogenesis using immunohistochemistry in the aged and neurodegenerative brains of SAMP8 mice, which is an animal model of accelerated senescence that mimics aging-related Alzheimer's pathology. Neurodegenerative processes observed in the brains of aged SAMP8 mice at 10 months of age include the presence of damaged neurons, disorganization in the layers of the brain cortex, alterations in neural processes and the length of neuronal prolongations and β-amyloid accumulation in the cortex and hippocampus. This neurodegeneration may be associated with neurogenic responses in the hippocampal dentate gyrus of these mice, since we observed a neurogenic niche of neural stem and progenitor/precursors cells in the hippocampus of SAMP8 mice. However, hippocampal neurogenesis seems to be compromised due to alterations in the cell survival, migration and/or neuronal maturation of neural precursor cells due to the neurodegeneration levels in these mice. Chronic treatment with melatonin for 9 months decreased these neurodegenerative processes and the neurodegeneration-induced neurogenic response. Noticeably, melatonin also induced recovery in the functionality of adult hippocampal neurogenesis in aged SAMP8 mice.
成年海马神经发生在衰老过程中和不同的神经精神和神经退行性疾病中发生改变。褪黑素在衰老和神经病理条件下显示出神经发生和神经保护特性。在这项研究中，我们使用免疫组织化学方法评估了慢性褪黑素治疗对 SAMP8 小鼠衰老和神经退行性大脑中不同神经退行性标记物和海马神经发生的影响，SAMP8 小鼠是一种加速衰老的动物模型，模拟与衰老相关的阿尔茨海默病病理。在 10 个月大的 SAMP8 年老小鼠大脑中观察到的神经退行性过程包括受损神经元的存在、大脑皮层层的紊乱、神经过程的改变以及神经元延长和β-淀粉样蛋白在皮层和海马中的积累。这种神经退行性变可能与这些小鼠海马齿状回的神经发生反应有关，因为我们观察到 SAMP8 小鼠海马中有神经干细胞和祖细胞/前体细胞的神经发生龛。然而，由于这些小鼠的神经退行性变水平，神经前体细胞的细胞存活、迁移和/或神经元成熟发生改变，海马神经发生似乎受到了损害。慢性褪黑素治疗 9 个月可减少这些神经退行性过程和神经退行性变诱导的神经发生反应。值得注意的是，褪黑素还诱导了衰老 SAMP8 小鼠成年海马神经发生功能的恢复。
