Serine Racemase in Inhibitory Neurons at Striatum and it Might be Involved in Schizophrenia's Pathophysiology with d1 and d2 Receptors

Abstract

Introduction

There is substantial evidence that hypofunction of the N-methyl-d-aspartate receptor (NMDAR) is a core pathophysiological mechanism underlying schizophrenia. d-serine and serine racemase (SR) (NMDAR co-agonist and it's producer) are thought to be involved in schizophrenia's pathophysiology as NMDAR function moderators. Our laboratory showed that excitatory neuron specific SR knock out (SRKO) mice still have just 50% reduction of SR whereas full SRKO mice had no SR. Furthermore d-serine and SR are found in inhibitory neurons not only in excitatory neurons with immunohistochemistry methods. Because NMDAR has excitatory functions, the existence of d-serine and SR in inhibitory neurons and their functions are of interest.

Aims

To elucidate the existence and roles of d-serine and SR in inhibitory neurons.

Methods

Inhibitory neuron marker, GAD65, specific conditional SRKO (GAD65 SRKO) mice were made by Cre-lox recombination method. The GAD65 SRKO mice were analyzed by HPLC for d-serine concentration, western blotting for SR expression, immunohistochemistry for SR positive cell's character identification and behavioral testing.

Results

GAD65 SRKO had about 50% reduction of SR in striatum but no reduction in hippocampus and frontal cortex. d-serine of GAD65 SRKO mice was not different from WT mice. Immunohistochemistry works revealed SR is in medium spiny neuron of striatum and has colocalization with DARRP-32, D1 receptor, and D2 receptor.

Conclusions

SR is expressed in inhibitory neurons at least in striatum. It might be involved in schizophrenia's pathophysiology because it colocalizes with D1 and D2 receptors.

Disclosure of interest

The authors have not supplied their declaration of competing interest.