Transport of Glucose by the Plasma Membrane Affects the Removal and Concentration of Ca at Rest in Neurons - Implications of a Condition Prior to Alzheimer's Disease?

Alzheimer's disease (AD) is classically characterized by two major markers: extracellular development of senile plaques and intracellular formation of neurofibrillary tangles. Nonetheless, neuronal glucose hypometabolism and Ca deregulation have been separately implied in the genesis and progress of the neurodegenerative process. In this sense, the goal of this study was to investigate if modifications in the glucose transport would influence the cellular viability and would be involved with the activity of Ca removal from the neuron. The total levels of plasma membrane Ca-ATPase (PMCA) and glucose transporters (GLUT1 and 3), as well as glucose entry and intracellular Ca dynamics were quantified in neurons maintained at different glucose concentrations or submitted to GLUT3 mRNA interference. The results showed that reduced extracellular glucose impaired neuronal viability from day 8, but didn't change the total protein levels of GLUT1, GLUT3 and PMCA before the onset of the cell death. Conversely, the rate of glucose transport and Ca concentration was already altered since the 4th day of external glucose reduction. Interestingly, reduction of GLUT3 on plasma membrane led to lower glucose transport and intracellular Ca accumulation. It was observed that the reduction of glucose transport directed the neuron to decrease the removal and increase of intracellular Ca at rest. Therefore, we concluded that reduced glucose transport impairs neuronal viability and compromise the activity of Ca removal from the neuron. Thus, it is expected that changes in glucose transport may lead to a more susceptible condition or trigger a neurodegenerative condition resulting in accumulation of intracellular Ca.