D-aspartate dysregulation in Ddo(-/-) mice modulates phencyclidine-induced gene expression changes of postsynaptic density molecules in cortex and striatum.
Progress in neuro-psychopharmacology & biological psychiatry October 1, 2015 Andrea De Bartolomeis, Francesco Errico, Giuseppe Aceto et al.
Elevated D-aspartate levels in mice altered expression of key postsynaptic density genes involved in glutamate signaling. In mice lacking D-aspartate oxidase (Ddo-/-), which have persistently high brain D-aspartate, Homer1a expression decreased in the prefrontal cortex, Homer1b/c increased in the striatum, and PSD-95 decreased in both striatum and cortex. Acute treatment with phencyclidine (PCP) restored and even potentiated Homer1a expression in the prefrontal cortex of these mutant mice but had limited effects on other genes. These findings suggest that sustained D-aspartate elevation may trigger adaptive changes in Homer1a that could explain protective effects against PCP-induced behavioral alterations.