Chronic Treatment with Melatonin Improves Hippocampal Neurogenesis in the Aged Brain and Under Neurodegeneration

Abstract

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.

Pathophysiology of Pleiotropic Effects and Prospects for the Use of Melatonin

“…Данный эффект блокируется конкурентным антагонистом рецепторов мелатонина, люзиндолом, в частности в нервных стволовых клетках и плюрипотентных стволовых клетках [29]. На уровне тотипотентных стволовых клеток действие МТ реализуется за счет защиты от окислительного, токсического и других форм клеточного стресса, ускорения созревания яйцеклеток [30,31].…”

Special Issue on “Pleiotropic Benefits of Melatonin: From Basic Mechanisms to Disease”

“…It is of paramount importance to note that melatonin levels and its receptors significantly and gradually decline in several organs over the life-span [ 9 , 10 ], which may favor both the progression of ageing, and the increased risk of suffering different pathologies. In this regard, there are many and varied studies that show that the exogenous administration of melatonin can be beneficial for dealing with different diseases and pathological and/or degenerative conditions [ 9 , 11 , 12 , 13 ]. Among the different published works, the revision study carried out by Wang and collaborators (2022) is noteworthy, in which the current evidence of the application of melatonin not only on periodontal treatment, but also on periodontitis-related systemic comorbidities is discussed.…”

“…Recently, we have demonstrated that melatonin induces a recovery in the functionality of adult hippocampal neurogenesis in aged and neurodegenerative brains of mice with accelerated senescence [ 13 ]. In this respect, Sun and collaborators (2022) also showed that melatonin promotes antler growth in sika deer by accelerating MT1-mediated mesenchymal cell differentiation and inhibiting VEGF-induced degeneration of chondrocytes [ 20 ].…”