Studying the Distribution, Release and Biosynthesis of D-Amino Acids

Besides well-known neurotransmitters such as serotonin and dopamine, amino acids underlie much of synaptic communication in our brain. Most research has focused on the role(s) that the more common l-enantiomers of amino acids play in neurotransmission and neuromodulation. However, recent findings indicate that several d-amino acids are present and involved in the mammalian brain, and that changes in the levels of these amino acids coincide with development of different diseases. Therefore, the neurochemistry of d-amino acids has become a new topic of interest to our group. In our experiments designed to uncover the functional roles of d-Asp and d-Glu in the brain, we use Aplysia californica.

While basic biochemistry textbooks state that in higher animals, the building blocks of life are l-amino acids, it appears that in the brain, there are exceptions. One established exception is the presence of the d-form of the amino acid serine (d-Ser), which modulates glutamate signaling. Our group and others have evidence for the presence of a second d-amino acid, d-Asp, in the nervous systems of a number of animals. Using a range of methods, we have shown that specific neurons can convert L-Asp to D-Asp and release this in a Ca-dependent manner, and we are currently measuring the electrophysiological effects of d-Asp.  Lastly, we have found several neurons that have high levels of d-Glu, while its levels in the entire brain appear to be low, indicating it may be another relevant d-amino acid in the brain.

D-Asp detection

Above: Detection of D-Asp in the cell soma and the processes of sensory neurons. (A) Image of an isolated sensory neuron. Electropherograms of D-Asp in (B) the processes and (C) the soma from a single pleural sensory neuron.

Relevant Publications:
H. Miao, S.S. Rubakhin, C.R. Scanlan, L. Wang, J.V. Sweedler, D-Aspartate as a putative cell-cell signaling molecule in the Aplysia californica central nervous system, J. Neurochem. 97, 2006, 595-606.

H. Miao, S.S. Rubakhin, J.V. Sweedler, Subcellular analysis of D-aspartate, Anal. Chem. 77, 2005, 7190-7194.