NITRIC-OXIDE SYNTHASE IN VENTRAL FOREBRAIN GRAFTS AND IN EARLY VENTRAL FOREBRAIN DEVELOPMENT

Embryonic ventral forebrain (VFB) grafts to cortex contain neurons tha t synthesize acetylcholine and partially ameliorate behavioral deficit s caused by excitotoxic damage to the nucleus basalis magnocelullaris in rats. An additional neurotransmitter, nitric oxide (NO), is synthes ized by a subset of cholinergic neurons in rat ventral forebrain. If t his neurotransmitter is expressed also by grafted cholinergic neurons (which include the embryonic medial septum and diagonal band), its fun ctional contribution should be considered. Six to twelve months after transplantation of embryonic VFB tissue rats were sacrificed. Brain ti ssue was processed either for in situ hybridization of nNOS and neurop eptide Y (NPY) or for immunohistochemistry of choline acetyltransferas e (ChAT) and neuronal nitric oxide synthase (nNOS). Quantification of messenger ribonucleic acid (mRNA) for nNOS was performed with radioact ively labeled probes (silver grains were counted) and a preliminary co mparison was made of graft sections to sections of the ventral forebra in of developing rats. Plots of silver grain counts against cell size revealed similar patterns in the grafts and in the ventral forebrain o f developing rats. The rates of expression of mRNA for nNOS in the gra fts were intermediate between those of the ventral forebrain of postna tal day 19 and those of postnatal day 12. Double immunohistochemical l abeling revealed that 45.87 + 8.26% of cells expressing ChAT also expr essed nNOS in the grafts, significantly higher than 33.16 + 3.9% which was the rate of co-expression observed in the adult ventral forebrain . This study suggests that possible contribution of NO to graft-associ ated modulation of behavior should be examined. (C) 1997 Elsevier Scie nce B.V.