Functions of brain L-aspartate and its derivatives on stress responses

L-Aspartate (L-Asp) functions as a neurotransmitter to stimulate the N-methyl-D-aspartate (NMDA) receptor (NMDA-R), one of the ionotropic L-glutamate receptors, even though its binding capacity for NMDA-R is weaker than L-glutamate. The amino acid L-Asp, as well as its enantiomer D-aspartate (D-Asp), occurs in the central nervous system of various species including chickens, pigeons, rats, mice and humans. D-Asp, synthesized from L-Asp by aspartate racemase, can also directly stimulate the NMDA-R. Furthermore, D-Asp may indirectly stimulate NMDA-R because it is a substrate for endogenous NMDA. Central injection of L-Asp and L-asparagine derived from L-Asp via transamidation decreased social separation-induced stress responses. In addition, central injection of NMDA can attenuate the stress responses while some reports indicate that stimulation of the NMDA-R has negative impacts on stress responses. Central L-Asp may act on stress responses not only directly but also via its metabolites, and the effects may depend on the type of stressors and/or brain regions.