FCGR2B knockdown alleviates diabetes-induced cognitive dysfunction by altering neuronal excitability

Area of Science:

• Neuroscience
• Endocrinology
• Immunology

Background:

• Diabetes mellitus (DM) significantly impacts cognitive function, affecting patients' quality of life.
• Diabetes-induced cognitive dysfunction is linked to altered neuronal excitability.
• Understanding the pathogenesis of DM-induced cognitive impairment is crucial for developing effective treatments.

Purpose of the Study:

• To investigate the role of Fc gamma receptor 2b (FCGR2B) in the pathogenesis of DM-induced cognitive impairment.
• To explore the molecular mechanisms underlying FCGR2B's involvement in cognitive dysfunction.
• To identify FCGR2B as a potential therapeutic target for DM-related cognitive decline.

Main Methods:

• A mouse model of diabetes mellitus was established using a high-fat diet and streptozotocin.
• Spatial learning and memory were assessed using the Morris water maze and novel object recognition tests.
• Protein expression of FCGR2B, SHC1, p-PI3K, and p-AKT was analyzed via Western blot; neuronal markers c-Fos and GABAA were detected by immunohistochemistry.

Main Results:

• Diabetic mice showed decreased spatial learning and memory, alongside elevated hippocampal FCGR2B expression, which correlated with SHC1 levels.
• Knockdown of FCGR2B in diabetic mice significantly improved cognitive function.
• FCGR2B silencing upregulated SHC1, p-PI3K, and p-AKT, increased the excitatory neuronal marker c-Fos, and decreased the inhibitory GABAA receptor in the hippocampus.

Conclusions:

• Knockdown of FCGR2B in the hippocampus of diabetic mice activates the PI3K/AKT signaling pathway via SHC1, alleviating cognitive impairment.
• Reducing FCGR2B levels ameliorates DM-induced cognitive deficits by modulating hippocampal neuronal excitability.
• FCGR2B emerges as a promising therapeutic target for treating cognitive dysfunction associated with diabetes mellitus.