Age-related changes in neuronal glucose uptake in response to glutamate and beta-amyloid

Energy supplies that may decline with age are crucial for cells to maintain ionic homeostasis and prevent neuron death. We examined baseline glucose transporter expression and rate of glucose uptake in cultured hippocampal neurons from embryonic, middle-age (12-month-old), and old (24-month-old) rats and exposed the neurons to glutamate, beta-amyloid, and mitochondrial inhibitors. Without stress, the rate of glucose uptake was similar in middle-age and old neurons, and the rate of glucose uptake in embryonic neurons was threefold greater than that in middle-age and old neurons. Glucose uptake increased in the presence of mitochondrial inhibitors (FCCP and oligomycin) for embryonic and middle-age neurons. The old neurons failed to increase glucose uptake. In the presence of glutamate, FCCP, and oligomycin, embryonic neurons showed a decrease in glucose uptake and the middle-age and old neurons showed no change in glucose uptake. Middle-age neurons took up significantly more glucose than old neurons when under mitochondrial and glutamate stress. In the presence of beta-amyloid, only embryonic neurons increased glucose uptake; middle-age and old neurons did not. Fluorescence imaging of immunoreactive glut3 in response to beta-amyloid demonstrated a 16-49% increase in glut3 immunoreactivity at the plasma membrane for the three ages. The results suggest that old neurons were not able to upregulate glucose uptake to ensure cell survival. Neuron aging does not indicate a defect in normal glut3 function; rather, our results suggest that mechanisms regulating glucose uptake under stress fail to react in time to ensure cell survival.