Specific Aim 1: To determine whether testosterone deprivation alone causes 1) brain insulin resistance by decreased neuronal insulin receptor function (insulin-induced LTD) and brain insulin signaling, 2) the impairment of synaptic plasticity by decreased hippocampal long-term potentiation (LTP), 3) the impairment of brain mitochondrial function, 4) decreased in hippocampal dendritic spines and 5) the cognitive decline.
Specific Aim 2: To investigate whether the combination of obesity induced by HFD consumption and the loss of testosterone accelerates brain insulin resistance, the impairment of synaptic plasticity, the impairment of brain mitochondrial function, decreased hippocampal dendritic spines, and cognitive decline, compared to those with obesity alone or those with testosterone deprivation alone.
Specific Aim 3: To investigate the effects of anti-diabetic drug DPP-4 inhibitor on brain insulin resistance, hippocampal synaptic plasticity, hippocampal dendritic spine formation, brain mitochondrial function and cognition in obese male rats induced by HFD consumption with or without testosterone deprivation.
Specific Aim 4: To investigate the effects of dietary intervention on brain insulin resistance including brain insulin receptor function and brain insulin signaling, hippocampal synaptic plasticity, hippocampal dendritic spine formation, brain mitochondrial function and cognition in obese male rats induced by HFD consumption with or without testosterone deprivation
