Modulation of d-Serine Levels in Brains of Mice Lacking PICK1

Background d -serine is an endogenous coagonist of the N -methyl- d -aspartate subtype glutamate receptor. Genetic association studies have implicated genes coding for enzymes associated with d -serine metabolism in schizophrenia and bipolar disorder. Methods Protein expression of serine racemase (SR) and its binding partner, protein interacting with C-kinase (PICK1), were examined by Western blotting in brains from wildtype and PICK1 knockout mice. Levels of d -serine in wildtype and PICK1 mice were also examined by an established high-pressure liquid chromatography protocol. Results Expression of SR and PICK1 proteins was developmentally regulated. Although no change was observed in the level of SR protein, levels of d -serine were selectively decreased in the forebrain of neonatal PICK1 knockout mice, compared with those in wildtype mice. Conclusions PICK1 may be involved in the regulation of brain d -serine levels and SR in a spatially and temporally specific manner.