Early-life Photoperiod Influences Depression-like Behavior, Prepulse Inhibition of the Acoustic Startle Response, and Hippocampal Astrogenesis in Mice.

Environmental factors during early life stages affect behavioral and physiological phenotypes in adulthood. We examined the effect of photoperiods during development on neurogenesis and affective behaviors during adolescence/adulthood using C57BL/6J mice. Mice were born and raised until weaning under long-day conditions (LDs) or short-day conditions (SDs), followed by a 12L12D cycle until adulthood. Adult mice born under SD showed a shorter latency to first immobility in the forced swim test when compared with the mice born under LD. The mice born under SD also exhibited significantly lower prepulse inhibition, which is a characteristic of schizophrenia. However, the mice exposed to SD and LD during the prenatal period only did not show differences in prepulse inhibition. At 4 weeks of age, there were less 5-bromo-2'-deoxyuridine (BrdU)-positive cells in the dentate gyrus (DG) of the hippocampus of mice born under SD when compared with mice born under LD. Double immunostaining showed that the mice born under SD showed less BrdU/glial fibrillary acidic protein (GFAP, an astrocyte marker) cells when compared with mice born under LD. Furthermore, expression of the glucocorticoid receptor in the DG was higher in mice born under SD, and the photoperiod-dependent changes in the number of BrdU-positive cells in the DG were abolished by administration of RU486, a glucocorticoid receptor antagonist. These results suggest that the photoperiod in early life alters astrogenesis in the hippocampus via the hypothalamic-pituitary-adrenal axis and may relate to affective behaviors in adulthood.

D-serine in glia and neurons derives from 3-phosphoglycerate dehydrogenase.

d-Serine is an endogenous ligand for NMDARs generated from l-serine by the enzyme serine racemase (Srr). Both neuronal and glial localizations have been reported for d-serine and Srr. 3-Phosphoglycerate dehydrogenase is an exclusively astrocytic enzyme that catalyzes the first committed step of l-serine biosynthesis. Using transgenic mice expressing enhanced green fluorescent protein under the Srr promoter and mice with targeted deletion of Srr or 3-Phosphoglycerate dehydrogenase, we demonstrate predominantly neuronal sources of d-serine dependent on astrocytic supply of l-serine. These findings clarify the cellular basis for the regulation of NMDAR neurotransmission by d-serine.