The serine racemase mRNA is expressed in both neurons and glial cells of the rat retina

Abstract

IntroductionD-Serine acts as an obligatory and endogenous coagonist for the N-methyl-D-aspartate (NMDA) receptorrelated glycine site in the mammalian brain (Hashimoto et al., 1993;Matsui et al., 1995;Schell et al., 1995;Hashimoto and Oka, 1997;Danysz and Parsons, 1998). D-Serine is synthesized by serine racemase (Srr), which converts L-serine to D-serine. The regional profile of Srr closely resembles those of endogenous D-serine and NMDA receptors, which are highest in the forebrain and lowest in the hindbrain (Yoshikawa et al., 2004). Previous immunohistochemical studies have demonstrated that D-serine and Srr were localized exclusively in glial fibrillary acidic protein (GFAP)-positive astrocytes (Hashimoto and Oka, 1997;Schell et al., 1997; Wolosker et al., 1999;Mustafa et al., 2004). However, recent studies using immunohistochemistry, Western blot, and in situ hybridization have demonstrated that D-serine (Yasuda et al., 2001;Puyal et al., 2006) and Srr (Kartvelishvily et al., 2006;Yoshikawa et al., 2006Yoshikawa et al., , 2007 are signifi cantly expressed in neurons of tissue sections, and of primary cultures of the rat brain as compared with astrocytes.Compared with the brain, the retina contains fewer cell types, many of which have recognizable morphologies and consistent positions, making any investigation of the mechanisms for the central nervous system more The serine racemase mRNA is expressed in both neurons and glial cells of the rat retina

Overexpression of serine racemase in retina and overproduction of D-serine in eyes of streptozotocin-induced diabetic retinopathy

“…Judging from morphology, these are glial cells containing strong SR staining. These may include Müller cells, astrocytes, or other glial cells in retina expressing SR [20,38,40]. Retinal homogenates also contained an SR dimer resistent to the denaturation conditions of SDS-PAGE, as we previously documented for microglia [16], though in much smaller amounts than monomers (not shown).…”

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

“…In addition to synaptic shaping, the source of d -serine release, neuronal vs glial, continues to be vigorously debated. We note that the cortical and hippocampal regions where neuronal-dominant d -serine release has been identified 47−49 also possess high SR and low DAO activity. 25,47,50 By contrast in the retina and cerebellum, where astrocytic d -serine release is demonstrably critical, 12,24,41,51−53 the relative enzyme contributions seem reversed, 16,54 raising the intriguing hypothesis that the tissue-specific balance of regulatory enzyme activity might influence the predominant site of d -serine release.…”

Inhibition of Human Serine Racemase, an Emerging Target for Medicinal Chemistry

“…It is present in Müller cells and astrocytes of rat retina [47]. Its presence in both retinal neurons and astrocytes was further confirmed on the mRNA level [43]. SR was studied in the rat vestibular sensory system [48], and it is present in Schwann cells and epineural fibroblasts of rat sciatic spinal nerve [49].…”

“…The cellular distribution of SR is controversial. It was first detected only in glial cells [42], but more recently it was reported to be present in neurons as well as glia [43][44][45]. In other studies, SR has been detected in protoplasmic astrocytes and pyramidal neurons of the hippocampus and cortex, in Purkinje cells, and in Bergmann glia of the cerebellum [33,46].…”