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Methionine Restriction Improves Cognitive Ability by Alleviating Hippocampal Neuronal Apoptosis through H19 in
Chuanxing Feng1,2, Yuge Jiang2, Shiying Li3
1State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China.
Abstract:
LncRNA H19 has been reported to regulate apoptosis and neurological diseases. Hippocampal neuron apoptosis damages cognitive ability. Methionine restriction (MR) can improve cognitive impairment. However, the effect of MR on hippocampal neuronal apoptosis induced by a high-fat diet (HFD) in middle-aged mice remains unclear. For 25 weeks, middle-aged mice (C57BL/6J) were given a control diet (CON, 0.86% methionine + 4.2% fat), a high-fat diet (HFD, 0.86% methionine + 24% fat), or an HFD + MR diet (HFMR, 0.17% methionine + 24% fat). The HT22 cells were used to establish the early apoptosis model induced by high glucose (HG). In vitro, the results showed that MR significantly improved cell viability, suppressed the generation of ROS, and rescued HT22 cell apoptosis in a gradient-dependent manner. In Vivo, MR inhibited the damage and apoptosis of hippocampal neurons caused by a high-fat diet, reduced hippocampal oxidative stress, improved hippocampal glucose metabolism, relieved insulin resistance, and enhanced cognitive ability. Furthermore, MR could inhibit the overexpression of H19 and caspase-3 induced by HFD, HG, or H2O2 in vivo and in vitro, and promoted let-7a, b, e expression. These results indicate that MR can protect neurons from HFD-, HG-, or H2O2-induced injury and apoptosis by inhibiting H19.
Insights
Methionine restriction (MR) protects middle-aged mice from high-fat diet-induced cognitive decline by reducing hippocampal neuron apoptosis. MR inhibits the long non-coding RNA H19, mitigating neuronal injury and oxidative stress.
Area of Science:
- Neuroscience
- Molecular Biology
- Nutritional Science
Background:
- Long non-coding RNA H19 is implicated in apoptosis and neurological disorders.
- Hippocampal neuron apoptosis negatively impacts cognitive function.
- Methionine restriction (MR) is known to ameliorate cognitive impairment.
Purpose of the Study:
- To investigate the protective effects of MR against high-fat diet (HFD)-induced hippocampal neuronal apoptosis in middle-aged mice.
- To elucidate the underlying molecular mechanisms involving LncRNA H19.
Main Methods:
- Middle-aged mice were fed control, HFD, or HFD + MR diets for 25 weeks.
- In vitro studies used HT22 cells to model high glucose (HG)-induced apoptosis.
- Assessed cell viability, reactive oxygen species (ROS) generation, apoptosis markers, oxidative stress, glucose metabolism, insulin resistance, and cognitive function.
Main Results:
- MR improved HT22 cell viability and reduced apoptosis and ROS generation in vitro.
- In vivo, MR protected hippocampal neurons from HFD-induced damage, reduced oxidative stress, and improved glucose metabolism and insulin resistance.
- MR enhanced cognitive ability and inhibited H19 and caspase-3 overexpression, while promoting let-7a, b, e expression.
Conclusions:
- Methionine restriction offers neuroprotection against HFD-induced neuronal injury and apoptosis.
- The protective mechanism involves the inhibition of LncRNA H19 and modulation of oxidative stress and metabolic pathways.
- MR demonstrates potential as a dietary intervention for cognitive health in aging populations exposed to detrimental diets.
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