The serine racemase mRNA is predominantly expressed in rat brain neurons

Abstract

D-serine is an endogenous and obligatory coagonist for the glycine site of the N-methyl-D-aspartate receptor in the mammalian brain. D-serine is synthesized from L-serine by serine racemase; immunohistochemical studies have long been believed to indicate that serine racemase and D-serine occur predominantly in astrocytes. However, we have recently demonstrated in the primary cultures that both the mRNA and protein levels of serine racemase are higher in neurons than in astrocytes. Here we report the application of in situ hybridization based on tyramide signal amplification for the detection of serine racemase mRNA in sections of the adult rat brain. Serine racemase mRNA could be demonstrated in a large number of neurons throughout the brain, especially in the forebrain such as the cerebral cortex, striatum, and hippocampus. This is the first study to demonstrate the exact localization of serine racemase mRNA at the cellular or tissue level. These results suggest that neuron-derived D-serine could modulate neurotransmission via the glycine site of N-methyl-D-aspartate receptors.

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

“…These results indicate that Srr mRNA is expressed in both neurons and glial cells of the retina, optic nerve head, and lamina cribrosa. These findings, together with the previous reports that Srr is distributed in neurons of the brain (Kartvelishvily et al, 2006;Puyal et al, 2006;Yoshikawa et al, 2007), suggest the possibility that the neuronderived D-serine could modulate neurotransmission via the glycine site of NMDA receptors in the retina.…”

“…Several lines of evidence support this possibility: 1) an immunohistochemistry study demonstrated that D-serine are present in amacrine cells in the rat retina (Yasuda et al, 2000); 2) an in situ hybridization study demonstrated that Srr mRNA is expressed in a large number of neurons throughout the brain, especially the forebrain such as the cerebral cortex, striatum and hippocampus (Yoshikawa et al, 2007); 3) HPLC analysis, real-time quantitative RT-PCR, in situ hybridization, and Western blot studies clearly demonstrated the presence of D-serine and Srr in neurons of the primary cultures (Kartvelishvily et al, 2006;Yoshikawa et al, 2006); 4) an immunohistochemistry study demonstrated that D-serine (Yasuda et al, 2001) and Srr (Kartvelishvily et al, 2006) are present in neurons of the rat brain, and 5) D-serine is mainly located in the neurons of vestibular nuclei in adult rats (Puyal et al, 2006).…”

“…Preparation of riboprobes for in situ hybridization was performed according to the method described by Yoshikawa et al, (2007). A nonradioactive in situ hybridization based on TSA was performed according to the method described by Yang et al (1999) with several modifi cations.…”

“…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 …”

The neurobiology of D-amino acid oxidase and its involvement in schizophrenia

“…Parenthetically, comparable unforeseen complexities regarding SRR have recently emerged. Initially viewed as being glial and cytosolic, 56 SRR is now believed to be partially, if not largely, neuronal 135,136 and to be prominently associated with the plasma membrane. 137,138 Moreover, redistribution between cytosol and membrane has a crucial role in the determination of SRR activity and its regulation by glutamate signalling.…”