Summary
- A study found that adult mice with Type 2 Diabetes exhibited deficits in spatial memory and nest-building abilities, as well as changes in exploratory behavior.
- Chronic measures leading to peripheral insulin resistance were linked to biochemical and functional impairments in the mouse brain.
- Transcriptomic analysis revealed significant gene expression changes in the cortex and hippocampus of mice with Type 2 Diabetes.
- Genes involved in inflammation, metabolism, blood-brain barrier integrity, and neurotransmission were found to be misregulated in the brains of mice with Type 2 Diabetes.
- Validation of gene expression changes at the mRNA and protein level confirmed alterations in certain genes associated with Type 2 Diabetes in the brain.
Chronic type 2 diabetes can lead to cognitive decline in mice, a recent study shows. Researchers found that adult mice with type 2 diabetes showed deficits in spatial memory and nest-building abilities compared to healthy mice. The study also revealed that diabetic mice spent more time in the open arm of an elevated plus maze, indicating lower anxiety levels.
The cognitive impairments observed in diabetic mice were linked to biochemical changes in the brain. Elevated levels of mTORC1 phosphorylated at Serine 2448 were found in diabetic mice, indicating insulin resistance. This phosphorylation affects cell growth, protein synthesis, and metabolism, leading to reduced insulin signaling.
To understand how type 2 diabetes affects brain function, researchers analyzed gene expression in the cortical and hippocampal regions of diabetic mice. They identified 28 genes in the cerebral cortex and 15 genes in the hippocampus that were significantly altered in diabetic mice. These genes are involved in inflammation, immunity, cellular rhythmicity, metabolism, blood-brain barrier integrity, oxidative metabolism, gene expression, cell-cell interaction, and neurotransmission.
Further experiments confirmed the changes in gene expression at the mRNA and protein levels. The study demonstrated that diabetic mice had altered protein levels of CLDN5 and IRF7 in the hippocampus and CLDN5 in the cerebral cortex. Additionally, the activation of NF-κB, a key regulator of the immune and inflammatory response, was observed in the brains of diabetic mice.
Researchers concluded that chronic insulin resistance in diabetic mice leads to both biochemical and functional impairments in the brain. The study highlights the importance of understanding the mechanisms underlying cognitive decline in diabetes and suggests potential targets for intervention to improve brain health in diabetic individuals.
In summary, the study provides valuable insights into the relationship between type 2 diabetes and cognitive decline. By unraveling the molecular changes occurring in the brain of diabetic mice, researchers have identified potential pathways that could be targeted to prevent or mitigate cognitive impairments associated with diabetes. Further research in this area could lead to the development of novel therapies for individuals with diabetes at risk of cognitive decline.
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Neurology, Diabetes & Endocrinology, Pathology & Lab Medicine