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Stem cell factor protects against neuronal apoptosis by activating AKT/ERK in diabetic mice
1Department of Neurology, Affiliated Drum Tower Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.
Abstract:
Neuronal apoptosis occurs in the diabetic brain due to insulin deficiency or insulin resistance, both of which reduce the expression of stem cell factor (SCF). We investigated the possible involvement of the activation of the MAPK/ERK and/or AKT pathways in neuroprotection by SCF in diabetes. Male C57/B6 mice (20-25 g) were randomly divided into four groups of 10 animals each. The morphology of the diabetic brain in mice treated or not with insulin or SCF was evaluated by H&E staining and TUNEL. SCF, ERK1/2 and AKT were measured by Western blotting. In diabetic mice treated with insulin or SCF, there was fewer structural change and apoptosis in the cortex compared to untreated mice. The apoptosis rate of the normal group, the diabetic group receiving vehicle, the diabetic group treated with insulin, and the diabetic group treated with SCF was 0.54 +/- 0.077%, 2.83 +/- 0.156%, 1.86 +/- 0.094%, and 1.78 +/- 0.095% (mean +/- SEM), respectively. SCF expression was lower in the diabetic cortex than in the normal cortex; however, insulin increased the expression of SCF in the diabetic cortex. Furthermore, expression of phosphorylated ERK1/2 and AKT was decreased in the diabetic cortex compared to the normal cortex. However, insulin or SCF could activate the phosphorylation of ERK1/2 and AKT in the diabetic cortex. The results suggest that SCF may protect the brain from apoptosis in diabetes and that the mechanism of this protection may, at least in part, involve activation of the ERK1/2 and AKT pathways. These results provide insight into the mechanisms by which SCF and insulin exert their neuroprotective effects in the diabetic brain.
Insights
Stem cell factor (SCF) protects the diabetic brain from neuronal apoptosis by activating MAPK/ERK and AKT pathways. Insulin treatment also increases SCF expression, enhancing these neuroprotective effects in diabetes.
Area of Science:
- Neuroscience
- Endocrinology
- Cell Biology
Background:
- Diabetes mellitus is associated with increased neuronal apoptosis in the brain.
- Insulin deficiency or resistance in diabetes reduces stem cell factor (SCF) expression, contributing to neurodegeneration.
- The role of SCF and its signaling pathways in diabetic neuroprotection requires further elucidation.
Purpose of the Study:
- To investigate the neuroprotective effects of stem cell factor (SCF) in the diabetic brain.
- To determine the involvement of MAPK/ERK and AKT pathways in SCF-mediated neuroprotection during diabetes.
- To examine the impact of insulin on SCF expression and related signaling pathways in the diabetic brain.
Main Methods:
- Utilized a mouse model of diabetes, randomly assigning animals into four groups: normal, diabetic (vehicle-treated), diabetic (insulin-treated), and diabetic (SCF-treated).
- Assessed brain morphology and neuronal apoptosis using Hematoxylin & Eosin (H&E) staining and TUNEL assay.
- Quantified the expression levels of SCF, phosphorylated ERK1/2 (p-ERK1/2), and phosphorylated AKT (p-AKT) via Western blotting.
Main Results:
- Diabetic mice exhibited significant cortical apoptosis and structural changes, which were reduced by insulin or SCF treatment.
- SCF expression was diminished in the diabetic brain cortex but restored by insulin.
- Phosphorylation of ERK1/2 and AKT pathways was decreased in diabetic mice, and this was reactivated by both insulin and SCF administration.
- Apoptosis rates were significantly lower in insulin-treated (1.86%) and SCF-treated (1.78%) diabetic mice compared to vehicle-treated diabetic mice (2.83%).
Conclusions:
- Stem cell factor (SCF) demonstrates significant neuroprotective effects against apoptosis in the diabetic brain.
- The neuroprotective mechanism of SCF in diabetes involves, at least partially, the activation of the MAPK/ERK and AKT signaling pathways.
- Insulin exerts neuroprotection in diabetes partly by upregulating SCF expression and subsequently activating these critical signaling cascades.
