Yamazaki, D., Horiuchi, J., Ueno, K., Ueno, T., Saeki, S., Matsuno, M., Naganos, S., Miyashita, T., Hirano, Y., Nishikawa, H., Taoka, M., Yamauchi, Y., Isobe, T., Honda, Y., Kodama, T., Masuda, T., Saitoe, M. (2014). Glial dysfunction causes age-related memory impairment in Drosophila.  Neuron 84(4): 753--763.

FBrf0226947

Research paper

Several aging phenotypes, including age-related memory impairment (AMI), are thought to be caused by cumulative oxidative damage. In Drosophila, age-related impairments in 1 hr memory can be suppressed by reducing activity of protein kinase A (PKA). However, the mechanism for this effect has been unclear. Here we show that decreasing PKA suppresses AMI by reducing activity of pyruvate carboxylase (PC), a glial metabolic enzyme whose amounts increase upon aging. Increased PC activity causes AMI through a mechanism independent of oxidative damage. Instead, increased PC activity is associated with decreases in D-serine, a glia-derived neuromodulator that regulates NMDA receptor activity. D-serine feeding suppresses both AMI and memory impairment caused by glial overexpression of dPC, indicating that an oxidative stress-independent dysregulation of glial modulation of neuronal activity contributes to AMI in Drosophila.