*3.1.3.1 D-serine*

Astrocytic D-serine is believed to play a role in neurogenesis. Obstruction of vesicle proliferation in astrocytes led to a decrease in dendritic formation in adultborn granule cells (abGCs) associated with a reduction in extracellular D-serine [72]. Further, mutations leading to decreases in D-serine result in changes reminiscent of SCZ. The DISC1 (disrupted-In-SCZ 1) gene is located on chromosome 1q42 and the product binds to and stabilizes serine racemase (SR), resulting in an increase in the conversion of L-Serine to D-Serine in astrocytes. A mutation in the DISC1 gene was first detected and linked to SCZ in a Scottish family with several major mental disorders, and now this gene mutation is recognized as a major risk factor for disorders involving abnormalities of neural development [74]. As a dominant-negative molecular tool, DISC1 mutants truncated at the C end of the full-length protein are used to elucidate the role of DISC1 in astrocytes [75]. In the mouse, dominant-negative C-terminus-truncated human DISC1 resulted in dendritic dysplasia and reduced neurogenesis [65]. Further, dominant-negative effects resulted in SR degradation, decreases in NMDA neurotransmission, and reductions in neurogenesis [65]. Further, this mutation appears to affect the neurogenesis of DG neurons more than other brain regions, such as the subventricular zone [76]. Therefore, it is tempting to speculate that D-serine depletion plays a role in SCZ.
