The free d-amino acid, d-aspartate, is abundant in the embryonic brain but significantly decreases after birth. Besides its intracellular occurrence, d-aspartate is also present at extracellular level and acts as an endogenous agonist for NMDA and mGlu5 receptors. These findings suggest that d-aspartate is a candidate signaling molecule involved in neural development, influencing brain morphology and behaviors at adulthood. To address this issue, we generated a knockin mouse model in which the enzyme regulating d-aspartate catabolism, d-aspartate oxidase (DDO), is expressed starting from the zygotic stage, to enable the removal of d-aspartate in prenatal and postnatal life. In line with our strategy, we found a severe depletion of cerebral d-aspartate levels (up to 95%), since the early stages of mouse prenatal life. Despite the loss of d-aspartate content, Ddo knockin mice are viable, fertile, and show normal gross brain morphology at adulthood. Interestingly, early d-aspartate depletion is associated with a selective increase in the number of parvalbumin-positive interneurons in the prefrontal cortex and also with improved memory performance in Ddo knockin mice. In conclusion, the present data indicate for the first time a biological significance of precocious d-aspartate in regulating mouse brain formation and function at adulthood.

Prenatal expression of d-aspartate oxidase causes early cerebral d-aspartate depletion and influences brain morphology and cognitive functions at adulthood / De Rosa, A.; Mastrostefano, F.; Di Maio, A.; Nuzzo, T.; Saitoh, Y.; Katane, M.; Isidori, A. M.; Caputo, V.; Marotta, P.; Falco, G.; De Stefano, M. E.; Homma, H.; Usiello, A.; Errico, F.. - In: AMINO ACIDS. - ISSN 0939-4451. - 52:4(2020), pp. 597-617. [10.1007/s00726-020-02839-y]

Prenatal expression of d-aspartate oxidase causes early cerebral d-aspartate depletion and influences brain morphology and cognitive functions at adulthood

Falco G.;Errico F.
2020

Abstract

The free d-amino acid, d-aspartate, is abundant in the embryonic brain but significantly decreases after birth. Besides its intracellular occurrence, d-aspartate is also present at extracellular level and acts as an endogenous agonist for NMDA and mGlu5 receptors. These findings suggest that d-aspartate is a candidate signaling molecule involved in neural development, influencing brain morphology and behaviors at adulthood. To address this issue, we generated a knockin mouse model in which the enzyme regulating d-aspartate catabolism, d-aspartate oxidase (DDO), is expressed starting from the zygotic stage, to enable the removal of d-aspartate in prenatal and postnatal life. In line with our strategy, we found a severe depletion of cerebral d-aspartate levels (up to 95%), since the early stages of mouse prenatal life. Despite the loss of d-aspartate content, Ddo knockin mice are viable, fertile, and show normal gross brain morphology at adulthood. Interestingly, early d-aspartate depletion is associated with a selective increase in the number of parvalbumin-positive interneurons in the prefrontal cortex and also with improved memory performance in Ddo knockin mice. In conclusion, the present data indicate for the first time a biological significance of precocious d-aspartate in regulating mouse brain formation and function at adulthood.
2020
Prenatal expression of d-aspartate oxidase causes early cerebral d-aspartate depletion and influences brain morphology and cognitive functions at adulthood / De Rosa, A.; Mastrostefano, F.; Di Maio, A.; Nuzzo, T.; Saitoh, Y.; Katane, M.; Isidori, A. M.; Caputo, V.; Marotta, P.; Falco, G.; De Stefano, M. E.; Homma, H.; Usiello, A.; Errico, F.. - In: AMINO ACIDS. - ISSN 0939-4451. - 52:4(2020), pp. 597-617. [10.1007/s00726-020-02839-y]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/832271
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