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Published on: March 23, 2011
Differential effects of melatonin on hippocampal neurodegeneration in different aged accelerated senescence prone
Shaowu Cheng1, Chunmei Ma, Huaigang Qu
1Department of Anatomy, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, China.
Objectives:
A purpose of this study is to compare the differential effects of melatonin on hippocampal neurodegeneration in accelerated senescence prone mouse-8 (SAMP8) which is initiated treatment at different age.
Methods:
The 4-months old SAMP8 mice were injected subcutaneously with melatonin (1 mg/kg/day) for 4 months. Similar treatments were performed in the 7-months old mice. When the animals were complete 11-months old, a series of tests were performed. Y maze test and Eight-arm radial maze task were used to assess cognitive performance. Hippocampal pyramidal cells were estimated by Nissl's staining. By using Gomori's methenamine silver methods, the methenamine silver staining granules (MSSG) were observed in area CA1 of hippocampus. A computer-assisted morphometric study was carried out on the ultrastructure of perikaryal CA1 pyramidal cell mitochondria. The volume density (Vv), surface density (Sv), numerical density (Nv) and mean volume (V) of the mitochondria were calculated.
Results:
Melatonin treatment obviously reduced the deposition of MSSG and elevated hippocampal pyramidal cell number while improving the learning and memory deficits of SAMP8. The mice initiated treatment from 4-months old exhibited a greater response to melatonin supplementation than 7-months old mice. It also decreased mean volume (V) and significantly elevated the Sv and Nv of the mitochondria in hippocampal CA1 region. However, 7-months old mice showed little effects on it.
Conclusions:
Our results indicate that the protective effects of melatonin on hippocampal neurodegeneration of SAMP8 are age dependent.
Insights
Early melatonin treatment in aging mice significantly protects against hippocampal neurodegeneration and cognitive decline. Younger mice showed greater benefits from melatonin supplementation, highlighting age-dependent effects.
Area of Science:
- Neuroscience
- Gerontology
- Pharmacology
Background:
- Accelerated senescence-prone mouse-8 (SAMP8) models exhibit age-related cognitive decline and hippocampal neurodegeneration.
- Melatonin, a hormone with antioxidant and anti-inflammatory properties, is investigated for its potential neuroprotective effects.
Purpose of the Study:
- To compare the differential effects of melatonin on hippocampal neurodegeneration in SAMP8 mice when treatment is initiated at different ages.
- To assess the impact of melatonin on cognitive function, neuronal survival, and mitochondrial ultrastructure in the hippocampus.
Main Methods:
- SAMP8 mice at 4 and 7 months of age received daily subcutaneous melatonin injections (1 mg/kg) for 4 months.
- Cognitive performance was evaluated using the Y-maze and Eight-arm radial maze tasks.
- Histological analyses included Nissl staining for pyramidal cell counts and Gomori's methenamine silver staining for MSSG deposition. Mitochondrial ultrastructure in CA1 pyramidal cells was assessed using morphometric analysis.
Main Results:
- Melatonin treatment reduced MSSG deposition, increased hippocampal pyramidal cell numbers, and improved learning and memory deficits in SAMP8 mice.
- Mice initiating melatonin treatment at 4 months old showed significantly greater neuroprotective and cognitive benefits compared to those starting at 7 months old.
- Melatonin modulated mitochondrial morphology in hippocampal CA1 neurons, decreasing mean volume and increasing surface and numerical density, with more pronounced effects in the younger treatment group.
Conclusions:
- The neuroprotective effects of melatonin against hippocampal neurodegeneration in SAMP8 mice are age-dependent.
- Initiating melatonin treatment earlier in life enhances its efficacy in mitigating age-related cognitive decline and neurodegenerative changes.
