Effects of the combined estrogen deprivation with obesity induced by high-fat diet consumption on neuronal insulin resistance, synaptic plasticity, cognition, brain oxidative stress and brain mitochondrial function
Specific aim 1To investigate the effects of time-course of estrogen deprivation combined with obesity induced by HFD on insulin resistance
1.1: To examine the effects of time-course of estrogen deprivation combined with obesity induced by HFD on insulin resistance on peripheral insulin resistance compared to that of estrogen deprivation alone or that of obesity induced by HFD alone by measuring the metabolic parameters
1.2: To examine the effects of time-course of estrogen deprivation combined with obesity induced by HFD on insulin resistance on neuronal insulin resistance compared to that of estrogen deprivation alone or that of obesity induced by HFD alone by measuring neuronal insulin receptor function in hippocampus (insulin-induced LTD) and brain insulin signaling
Specific aim 2 To investigate the effects of time-course of estrogen deprivation combined with obesity induced by HFD on cognitive function compared to that of estrogen deprivation alone or that of obesity induced by HFD alone, by using the Morris Water maze test
Specific aim 3 To investigate the effects of time-course estrogen deprivation combined with obesity induced by HFD on synaptic plasticity, compared to that of estrogen deprivation alone or that of obesity induced by HFD alone by measuring the phenomenon of hippocampal long-term potentiation, post-synaptic NMDAR/AMPAR currents and the density of dendritic spine.
Specific aim 4 To investigate the effects of time-course of estrogen deprivation combined with obesity induced by HFD compared to that of estrogen deprivation alone or that of obesity induced by HFD alone on brain oxidative stress by measuring MDA levels, and brain mitochondrial function by measuring mitochondrial reactive oxygen species (ROS) production, mitochondrial membrane potential change and mitochondrial swelling
