Neuroscience 2020 Apr 01;431:52-63. doi: 10.1016/j.neuroscience.2020.01.048.

Transport of Glucose by the Plasma Membrane Affects the Removal and Concentration of Ca2+ at Rest in Neurons - Implications of a Condition Prior to Alzheimer''s Disease?

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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 Ca2+ 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 Ca2+ removal from the neuron. The total levels of plasma membrane Ca2+-ATPase (PMCA) and glucose transporters (GLUT1 and 3), as well as glucose entry and intracellular Ca2+ 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 Ca2+ 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 Ca2+ accumulation. It was observed that the reduction of glucose transport directed the neuron to decrease the removal and increase of intracellular Ca2+ at rest. Therefore, we concluded that reduced glucose transport impairs neuronal viability and compromise the activity of Ca2+ 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 Ca2+.

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Genes referenced: LOC115919910 LOC581395 pmca