NUTRITIONAL INSULT AND RECOVERY IN THE NEONATAL RAT CEREBELLUM - INSULIN-LIKE GROWTH-FACTORS (IGFS) AND THEIR BINDING-PROTEINS (IGFBPS)

Alterations in growth caused by neonatal malnutrition may be mediated in part by changes in insulin-like growth factor (IGF) and IGF binding protein (IGFBP) expression. Since the neonatal rat cerebellum undergo es a transient, proliferative growth phase in the first two weeks of l ife, this structure was used to determine whether alterations in circu lating and tissue IGFs and IGFBPs may mediate effects of impaired nutr ition on the developing central nervous system. Gravid rats were place d on a 4% (protein-calorie deprived, D) or 20% (control, C) protein di ets one day prior to delivery and allowed to nurse their pups postpart um. Pups nursing from D mothers received a limited volume of milk and were calorically deprived. Some litters of D pups were foster fed by C mothers from day 8 to day 13 to constitute a recovery group (R). Cere bellar weight, protein, and DNA content in D pups were less than C, p < 0.001. In R pups, DNA and protein returned to C levels by day 13. Be tween days 6 and 13, serum IGF-I levels rose from 158 +/- 18 to 210 +/ - 18 ng/ml in C but remained low in D (47 +/- 6 ng/ml and 25 +/- 3 ng/ ml), respectively. In R pups, serum IGF-I partially recovered during t his time, and increased from 49 +/- 5 to 110 +/- 7 ng/ml. In cerebella r extracts, IGF-I levels in both C and D were lower at 13 days than at 6 days, p < 0.05 and p < 0.005, respectively. IGF-I levels in C were similar at day 9 and day 11 and were consistently higher than D (11.84 +/- 0.83 vs 8.56 +/- 0.92 ng/g, p < 0.02 C vs D). In R, IGF-I was red uced on day 11, but was similar to C on day 13. Serum IGF-II in D was lower than C, p < 0.01, and did not increase in the R group. Cerebella r IGF-II was virtually undetectable in either group. Immunoprecipitati on and ligand blotting studies of serum demonstrated that circulating levels of 32-34 K IGFBPs were increased 3-4 fold in D vs C, reflecting high levels of IGFBP-1 and/or -2, while levels of 24 K IGFBP-4 were l ower in D vs C. By contrast, immunoprecipitation and ligand blotting o f,cerebellar extracts detected IGFBP-2 and -4, but did not detect IGFB P-1. Further, tissue levels of IGFBP-2 were not increased in D vs C, a nd levels of IGFBP-4 also were not markedly affected by nutritional de privation. These results suggest that alterations in tissue content an d the availability of IGF-I only modestly contributed to the effects o f impaired nutrition in the developing central nervous system.