TDK conference 2017

Amino acids are the building blocks of proteins, and they also play important role as neurotransmitters in animals. Earlier it was thought that only their L-enantiomers are functional in higher animals, the D-conformation versions are results of the synthesizing enzyme’s malfunction. Nowadays it has been proven, that the free form of their D-enantiomers also occurs in high concentration in animals, playing a functional role under natural circumstances. In mammals, D-serine and D-Aspartate are the two D-amino acids that occur in the highest concentration and they function in the brain as neurotransmitters. These two D-amino acids are act as co-agonist of the NMDA receptors in the central nervous system, but showing a different distribution over brain regions. D-Serine is found in high concentration in the forebrain, and have been shown that its absence plays role in the development of schizophrenia. D-Aspartate is found in the hippocampus, where it improves of learning and memory processes. Neither the exact mechanism of their cognitive effect, nor their role in short-, medium- and long-term memory is known. In our experiments, we investigated how the chronic consumption of D-amino acids affects spatial learning and memory in mice. Spatial memory was measured using the hidden platform version of Morris water maze training and test. Plus maze test was used to measure how the D-amino acid consumption influences the exploratory behavior. Tests were performed on young adult male C57Bl mice. The treated animals consumed D-amino acids dissolved in their drinking water for 6 weeks. Based on a detailed evaluation of the water maze results, we could separate the effects of D-amino acids on short- (10-15 minutes) medium- (3-4 hours) and long-term (16 hours) memory. As a result of the tests we found that in the medium term, D-Aspartate treated animals remembered better to the place of the hidden platform than the control and the D-Serine treated groups. However both D-amino acid consuming groups showed less behavioral plasticity when the location of the platform was changed. The result of the plus maze experiment showed that the exploratory behavior of the D-Aspartate treated animals’ increased compared to the control group. Thus, D-Aspartate proved to be memory stimulating at 3-4 hours interval, which corresponds to the first wave of de novo protein synthesis. It is expected that D-Aspartate is primarily involved in the cognition through mechanisms relevant to the translational processes that take place hours after behavioral training.