Monoclonal antibodies against a dopamine-releasing protein (DARP) arrest fetal development, decrease brain...

Monoclonal antibodies (MAb) were produced against a partially purified dopamine-releasing protein (DARP) to examine the feasible physiological role of this factor during the development of the rat. These IgM isotype MAbs, and not other IgM antibodies (controls), induced a remarkable increase in fetal resorption and stillbirth rate and impaired the developmental increase of catecholamine concentration in the corpus striatum and hypothalamus of newborn rats. Neonatal injections of the anti-DARP MAb (a single injection of 200 mug, 24 h after birth or 40 mug on alternate days during the first 10 days) decreased the dopamine (DA) concentration of the corpus striatum by 30% on Day 10 and 15% on Day 25 and drastically impaired (by 43% on Day 25) the developmental increase in hypothalamic DA. Furthermore, in the hypothalamus, there was a marked decrease in epinephrine and an increase in norepinephrine (NE) concentration, suggesting an impairment in PNMT function. Neonatal anti-DARP injections also resulted in increased adrenal weight (45 and 44% on Days 10 and 25, respectively) and elevated NE content (anti-DARP, 315 +/- 12 ng, vs control, 223 +/- 16 ng, n = 6). Intrafetal injection of anti-DARP MAb (40 mug) on E 17 resulted in increased resorption and stillbirth accounting for 83% fetal loss. A 10-mug dose of the antibody produced 33% of fetal resorption or stillborn fetuses, whereas control injections resulted in only 4.4% of fetal loss. These data strongly suggest that DARP may be a neurotrophic factor involved in the growth and differentiation of central catecholaminergic neurons and probably necessary for the maturation of PNMT during the early development of rat brain.