Experts discover a new neurotransmitter with potential applications in the treatment of neurological diseases

The research paper, published in the Journal of Federation of American Societies for Experimental Biology (The FASEB Journal), is authored by Jordi García-Fernàndez, Salvatore D'Aniello and Ildiko Somorjai, from the UB's Department of Genetics and the Institute of Biomedicina of the University of Barcelona (IBUB), and by Enza Topo and Antimo D'Aniello, from the Department of Neurobiology of the Anton Dohrn Zoological Research Station in Naples.

D-Asp is an amino acid that was discovered in 1977 in the brains of squid and octopus by a research group coordinated by Antimo D'Aniello (Zoological Research Station, Naples). Since its discovery, this molecule has been the subject of several studies carried out in Italy and around the world. The article published in the FASEB Journal provides the first description of the activity of D-aspartic acid as a neurotransmitter in two evolutionary distinct animal species: the brown rat (Rattus norvergicus) and the European squid (Loligo vulgaris).

Salvatore D'Aniello, first author of the article, explains that, "The first chemical neurotransmitters were discovered some 40 years ago, but until now no study had made such a simple but novel discovery. D-Asp is no different to other classic amino acid neurotransmitters such as serine or glutamate, which have already been extensively researched." Neurotransmitters are molecules that transmit chemical signals in the nervous system. Synaptic transmission, which can be either electrical or chemical, is facilitated by 20 chemical neurotransmitters, including amino acids (L-glutamine, GABA) peptides (copamine, noradrenaline, vasopressin, insulin), amines (adrenaline, serotonin) or gases (nitric oxide, sulphuric acid).

"In our study," explains Salvatore D'Aniello, "we found that D-Asp meets all of the criteria that characterize biological molecules that exhibit neurotransmitter activity: they are present in high concentrations in the synaptic vesicles of axon terminals; synthesis for this amino acid occurs in neurons by conversion of L-Asp to D-Asp viaD-aspartate racemase; depolarization of nerve endings with potassium ions evokes an immediate release of D-Asp in a Ca²⁺ dependent manner; specific receptors for D-Asp occur at the postsynaptic membrane; and stimulation of nerve endings with D-Asp triggers signal transduction by increasing the second messenger cAMP." D-Asp plays an important role in the initial phases of central nervous system development in vertebrates and invertebrates. In humans, mice and chicken, large quantities of this molecule are produced in the brain during embryonic development.

After birth, D-Asp falls to minute levels and remains like this throughout adult life. Evidence suggests that the molecule is involved in the learning process and memory function in rats and enhances the cognitive capabilities of animals in a range of experiments. According to professor Jordi García-Fernàndez, "Basic research leads to advances in applied work by describing new functional mechanisms that explain the complex biological machinery of the nervous system. This study is of particular interest in the field of dementia, as it describes a novel neurotransmitter with a potential use in the treatment of certain neurological diseases (Parkinson's disease, schizophrenia, etc.)."

For the project reported in the FASEB Journal, the team from the UB's Department of Genetics analysed D-Asp content in the central nervous system of animal models, performed immunohistochemical analyses and carried out the comparative study. Although no further study of D-Asp in humans is planned in the short term, the UB team is working towards a new, related challenge: to isolate the specific receptor for D-Asp, an achievement that would represent a huge step forward in the development of possible therapeutic applications.