Thyroid hormone improves insulin signaling and reduces the activation of neurodegenerative pathway in the hippocampus of diabetic adult male rats

Aims: Diabetes mellitus (DM) and impairments of glucose metabolism and insulin resistance in the brain have been suggested as a likely etiology of Alzheimer's disease (AD). Studies have shown that thyroid hormones (THs) improve insulin sensitivity in DM rats and act as mediators of the plasticity of the nervous system altering behavior and cognitive function. Based on these findings, this study aimed to evaluate the effects of diabetes and triiodothyronine (T3) treatment upon proteins associated with DM and AD in the central nervous system. Main methods: Euglycemic and Diabetic (alloxan-induced) male Wistar rats were daily treated with T3 (1.5 mu g/100 g body weight) or vehicle (saline) for a 4-week period and subdivided into the following groups: euglycemic treated with saline (Control = C); diabetic treated with saline (Diabetic = D); euglycemic treated with T3 (T3); diabetic treated with T3 (DT3). The expression of insulin signaling, neurodegenerative and neuron survival markers was evaluated in the hippocampus by immunoblotting, ELISA, and RT-PCR. Key findings: T3 treatment decreased glycemia, restored the insulin signaling and reduced the activation of glycogen synthase kinase 3 (GSK3) and tau proteins content in the hippocampus of diabetic rats. Significance: The present data provide evidence that T3 treatment of diabetic rats is able to improve insulin sensitivity and reduce the activation of the neurodegenerative pathway in the brain, which might provide neuroprotection in this experimental model. (AU)