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The lack of dystrophin affects neurophysiological processes from the uterine phase, impacting neural circuitry in brain regions such as the prefrontal cortex, hippocampus, and cerebellum. This leads to reduced inhibitory GABAergic transmission and altered hippocampal glutamatergic signaling. The resulting imbalance between inhibitory and excitatory inputs contributes to the neurodevelopmental and cognitive deficits observed in DMD. Recent studies have reported correlations between serum levels of D\u2010aspartate and D\u2010serine, endogenous ligands of glutamatergic receptors, and conditions such as schizophrenia, spinal muscular atrophy, and aging. Furthermore, in a recent clinical study, we reported a general dysregulation of D\u2212\/L\u2010amino acids known to modulate glutamatergic neurotransmission in the serum of DMD patients, with significant correlations between muscle wasting, motor impairment, and alterations in L\u2010glutamate levels and the L\u2010glutamine\/L\u2010glutamate ratio. To delve deeper into this matter, we conducted an extensive neurochemical analysis using high\u2010pressure liquid chromatography to measure the levels of the same D\u2212\/L\u2010amino acids across various brain regions, the spinal cord, and serum of the\n                    <jats:italic>mdx<\/jats:italic>\n                    mouse model of DMD. Our results revealed a significant reduction in prenatal D\u2010aspartate levels and postnatal levels of specific L\u2010amino acids in the hippocampus of dystrophic mice compared to wild type. In adult\n                    <jats:italic>mdx<\/jats:italic>\n                    mice, we also observed a near\u2010significant decrease in hippocampal D\u2010serine levels and a significant reduction in spinal cord D\u2010aspartate levels. This study provides the first evidence potentially linking D\u2010\/L\u2010amino acid dysmetabolism in the hippocampus to the described neurophysiological alterations. Although further investigations are essential to validate this hypothesis, the mechanisms proposed here offer insight into how amino acid imbalances may contribute to the DMD\u2010associated neurological and cognitive deficits, thus supporting the rationale for developing future targeted therapeutic strategies.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc70223-gra-0001-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  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