Abstracts

Neural precursors persist throughout life in the rodent forebrain subventricular zone (SVZ). These precursors generate neuroblasts that migrate along the rostral migratory stream (RMS) to the olfactory bulb to form interneurons. The mechanisms underlying this process are not well understood. Retinoic acid (RA), a derivative of vitamin A (retinol) and an important regulator of embryonic neural development, is a candidate for regulating postnatal neurogenesis based on the expression pattern of retinoid receptors, binding proteins and synthesizing enzymes.
Sagittal slices of 250 mm thickness from postnatal day 2 (P2) mice were cultured for 4 days with different treatments. Cell proliferation was detected by adding BrdU into cultures and immunostaining.
We found that RA or retinol added to slice cultures increased SVZ-olfactory bulb neurogenesis in a dose-dependent manner. RA did not reduce cell death in this pathway assayed by TUNEL staining. Inhibitors of endogenous RA synthesis decreased neurogenesis in SVZ-olfactory bulb pathway, and electroporation of dominant-negative retinoid receptors inhibited SVZ cell differentiation and migration to the olfactory bulb.
These findings indicate that RA stimulates SVZ neuroblast proliferation and differentiation, but not survival, in the postnatal mouse forebrain. The influence of RA on forebrain neurogenesis in vivo and of other molecules involved in RA signaling in the postnatal SVZ will be further investigated.
[Supported by: NIH Grant: NS42143 and the Epilepsy Fundation of America]