Hyperglycemia plays a critical role in the development of
diabetic neuropathy.
Hyperglycemia induces oxidative stress in neurons, resulting in neuronal cell apoptosis and dysfunction. Anti-apoptotic properties of
neurosteroids have been demonstrated in numerous cellular models of neurodegenerative studies. Here, the protective effects of
neurosteroid allopregnanolone were investigated in in vitro and in vivo models of
diabetic neuropathy. The data show that
glucose decreased the viability of PC12 cells in a concentration-dependent manner.
Allopregnanolone at concentrations of 2.5, 5 and 10μM markedly prevented high
glucose-induced toxicity in naïve and
NGF-treated (neuron-like) PC12 cells. Furthermore, treatment of diabetic rats with
allopregnanolone (5 and 20mg/kg) significantly ameliorated diabetic-induced
thermal hyperalgesia. Moreover, this
neurosteroid inhibited
caspase 3 and decreased Bax/Bcl2 ratio in high
glucose-treated cells and spinal cord of diabetic rats. In conclusion, the data revealed that
allopregnanolone has protective effects against hyperglycemic-induced cellular damage and prevention of cell apoptosis is involved in its mechanisms. Our findings suggest that
allopregnanolone has protective effect against pro-apoptotic challenges such as diabetes and
hyperglycemia and propose therapeutic potential of
neurosteroids in attenuation of diabetic side effects such as neuropathy.