The Postnatal Development of d-Serine in the Retinas of Two Mouse Strains, Including a Mutant Mouse with a Deficiency in d-Amino Acid Oxidase and a Serine Racemase Knockout Mouse

Abstract

d-Serine, an N-methyl d-aspartate receptor coagonist, and its regulatory enzymes, d-amino acid oxidase (DAO; degradation) and serine racemase (SR; synthesis), have been implicated in crucial roles of the developing central nervous system, yet the functional position that they play in regulating the availability of d-serine throughout development of the mammalian retina is not well-known. Using capillary electrophoresis and a sensitive method of enantiomeric amino acid separation, we were able to determine total levels of d-serine at specific ages during postnatal development of the mouse retina in two different strains of mice, one of which contained a loss-of-function point mutation for DAO while the other was a SR knockout line. Each mouse line was tested against conspecific wild type (WT) mice for each genetic strain. The universal trend in all WT and transgenic mice was a large amount of total retinal d-serine at postnatal age 2 (P2), followed by a dramatic decrease as the mice matured into adulthood (P70–80). SR knockout mice retinas had 41% less d-serine than WT retinas at P2, and 10 times less as an adult. DAO mutant mice retinas had significantly elevated levels of d-serine when compared to WT retinas at P2 (217%), P4 (223%), P8 (194%), and adulthood (227%).

Electroretinographic Abnormalities and Sex Differences Detected with Mesopic Adaptation in a Mouse Model of Schizophrenia: A and B Wave Analysis

“…It has been shown that SR and D-serine expression normally changes dynamically in the retina with age, with D-serine being abundant earlier in development and declining in the first month of life. 76 In comparison to infant mice (3 weeks old), the adult mouse retina had limited Dserine and SR expression. 77 At present, it is not known why serine racemase and D-serine are so abundant early in development.…”

Improving the sensitivity in chiral capillary electrophoresis

“…LIF is the detection system which offers the best sensitivity of all the detectors used in CE and an evidence of this is the low LODs depicted in Table , generally in the nanomolar range even though the reported works did not employ additional preconcentration strategies . Moreover, in a recent published review article, it was demonstrated that LIF has been the most employed detector system in CE to determine chiral neuroactive molecules (e.g.…”

“…Thus, derivatization agents must offer high stability, minimal hydrolysis products, low reaction times, and be compatible with the excitation source employed. In recent years, the most employed derivatization agents have been 7‐fluoro‐4‐nitro‐2,1,3‐benzoxadiazole (NBD‐F) , followed by naphthalene‐2,3‐dicarboxaldehyde , and FITC []. Moreover, carboxytetramethylrhodamine succinimidyl ester was employed as a novel reagent to derivatize amino acids, although LODs values were not reported.…”

“…Authors found d ‐aspartic acid and d ‐serine in all the analyzed samples, being d ‐serine more concentrated than d ‐aspartate in an order of magnitude. Another interesting work reported the application of an EKC‐LIF method to the determination of the NBD‐labeled amino acid d ‐serine in retinas to study the postnatal development of this neurotransmitter in mice with deficiencies in serine racemase and d ‐amino acid oxidase . Thanks to this sensitive methodology (having LODs in the nanomolar range) serine enantiomers could be determined and quantified in most of the analyzed samples being this neurotransmitter more concentrated in mice with deficiencies in d ‐amino acid oxidase when compared to wild type mice.…”

Recent advances in amino acid analysis by capillary electromigration methods, 2013–2015

“…In mouse retina, levels of D‐Ser depend on its regulator enzymes (D‐amino acid oxidase, serine racemase), which are involved in the brain development. D‐Ser concentrations are quantified during the postnatal development in two different transgenic mice, one of which contained a loss‐of‐function point mutation for D‐amino acid oxidase while the other was a serine racemase knockout line . The total retinal D‐Ser is in a large amount at postnatal age and decreases as the mice matured into adulthood for wild and transgenic mice.…”