Mitochondrial Dysfunction in an Animal Model of Diabetic Neuropathy Is Associated with a Reduction of Neurosteroid Synthesis

The 2018 study by Stephen R. Humble investigated the relationship between mitochondrial dysfunction and reduced neurosteroid synthesis in an animal model of diabetic neuropathy. Using mice with type-II diabetic neuropathy and wild type controls aged 60-80 days, the study found that diabetic neuropathy was associated with mitochondrial dysfunction, leading to a decrease in the production of neurosteroids, molecules that modulate neuronal excitability and inflammation. The study also found an exaggerated effect of diazepam on GABAergic inhibitory tone in diabetic mice, likely due to physiological upregulation of key neurosteroidogenic enzymes in response to reduced pregnenolone synthesis by the mitochondria. The study concluded that mitochondrial dysfunction may play a significant role in diabetic neuropathy, and enhancing the GABAergic neurosteroid tone could potentially be of therapeutic benefit.