New insights on the influence of free d-aspartate metabolism in the mammalian brain during prenatal and postnatal life |
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| Affiliation: | 1. Universidad de Buenos Aires - Consejo Nacional de Investigaciones Científicas y Técnicas, Instituto de Química y Fisicoquímica Biológicas “Profesor Alejandro C. Paladini” (IQUIFIB), Facultad de Farmacia y Bioquímica, Buenos Aires, Argentina;2. Departamento de Bioquímica, Facultad de Química, Universidad Nacional Autónoma de México, Mexico;1. Facultad de Química y Biología, Departamento de Biología, Universidad de Santiago de Chile, USACH, PO 9170022, Santiago, Chile;2. Facultad de Medicina, Departamento de Neurología, Pontificia Universidad Católica de Chile, PO 8330024, Santiago, Chile;3. Facultad de Ingeniería, Departamento de Ingeniería Informática, Universidad de Santiago de Chile, USACH, PO 9170022 Santiago, Chile;4. Facultad de Medicina, Universidad Diego Portales, PO 8370007, Santiago, Chile;1. Laboratory of Molecular and Translational Psychiatry, Unit of Treatment Resistant Psychosis, Section of Psychiatry, University of Naples Federico II, Italy;2. Lundbeck LLC, Deerfield, IL, USA;1. Department of Physiotherapy & Rehabilitation, Tangdu Hospital, Fourth Military Medical University, Xi''an 710032, Shaanxi, PR China;2. Department of Psychiatry, Xi''an Mental Health Center, Xi''an 710061, Shaanxi, PR China;3. Department of Neurology, Tangdu Hospital, Fourth Military Medical University, Xi''an 710032, Shaanxi, PR China;4. Department of Endocrinology, Tangdu Hospital, Fourth Military Medical University, Xi''an, 710032, Shaanxi, PR China |
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| Abstract: | Free d-aspartate is abundant in the mammalian embryonic brain. However, following the postnatal onset of the catabolic d-aspartate oxidase (DDO) activity, cerebral d-aspartate levels drastically decrease, remaining constantly low throughout life. d-Aspartate stimulates both glutamatergic NMDA receptors (NMDARs) and metabotropic Glu5 receptors. In rodents, short-term d-aspartate exposure increases spine density and synaptic plasticity, and improves cognition. Conversely, persistently high d-Asp levels produce NMDAR-dependent neurotoxic effects, leading to precocious neuroinflammation and cell death. These pieces of evidence highlight the dichotomous impact of d-aspartate signaling on NMDAR-dependent processes and, in turn, unveil a neuroprotective role for DDO in preventing the detrimental effects of excessive d-aspartate stimulation during aging. Here, we will focus on the in vivo influence of altered d-aspartate metabolism on the modulation of glutamatergic functions and its involvement in translational studies. Finally, preliminary data on the role of embryonic d-aspartate in the mouse brain will also be reviewed. |
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