Modulation of d-Serine Levels in Brains of Mice Lacking PICK1
Received 19 September 2007; received in revised form 25 September 2007; accepted 25 September 2007. published online 15 January 2008.
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.
ABSTRACT