Stability of local brain levels of insulin-like growth factor-I in two well-characterized models of decreased plasma IGF-I

Abstract

Insulin-like growth factor-I (IGF-I), a functionally important neurotrophic factor, impacts tissues throughout the body including the central nervous system. In addition to the significant proportion of IGF-I that is synthesized in the liver and released into the plasma, IGF-I is expressed locally in tissues. The present study investigated the relationship between plasma and local brain levels of IGF-I in two well-characterized models of decreased IGF-I. The first is an adult-onset growth hormone deficiency (AOGHD) model, and the second is a caloric restriction (CR) model. In the first cohort of animals from both models, the hippocampus was removed from the brain immediately following decapitation, and in the second cohort, the animals were perfused transcardially with phosphate buffered saline to remove cerebral blood prior to harvesting the hippocampus. Our results demonstrated that although the plasma IGF-I levels were decreased in the CR and AOGHD rats compared to controls, the hippocampal IGF-I levels did not differ among the groups. These data suggest that local brain IGF-I levels are regulated in a different manner than plasma IGF-I levels.

Figure 1

Adult-onset GH deficiency model. (A) GH deficient (GH2−) groups have significantly lower mean body weights than heterzygous (HZ) and GH replete (GH+) groups. Perfused and non-perfused cohorts do not differ in any group. *p < 0.001 GH− compared to GH+ and HZ. (B) Hippocampal weight does not differ among HZ, GH+ and GH− groups. (C) Pituitary levels of GH in GH+ and GH− groups are significantly lower compared to the HZ group. Perfused and non-perfused cohorts do not differ in any group. *p < 0.001 GH− and GH+ compared to HZ. (D) Plasma IGF-I levels are significantly lower in GH− than in GH+ and HZ rats, but do not differ between perfused (cardiac blood) and non-perfused (trunk blood) in any group. *p < 0.001 GH− compared to GH+ and HZ. (E) In non-perfused hippocampus, the IGF-I level in GH− rats is significantly lower than in GH+ and HZ rats. In contrast, in perfused hippocampus, IGF-I levels do not differ among groups, but in each group are significantly lower than in non-perfused hippocampus. *p < 0.001 non-perfused hippocampus GH− compared to GH+ and HZ; #perfused GH−, GH+, and HZ groups compared to non-perfused GH−, GH+, and HZ groups.

Figure 2

Caloric restriction model. (A) CR groups have significantly lower mean body weights than AL fed groups. Perfused and non-perfused cohorts do not differ in any group. *p < 0.001 CR compared to AL. (B) Hippocampal weight does not differ between the AL and CR groups. (C) Plasma IGF-I levels are significantly lower in CR than in AL rats, but do not differ between perfused (cardiac blood) and non-perfused (trunk blood) in any group. *p < 0.001 CR compared to AL. (D) In non-perfused hippocampus, the IGF-I level in CR rats is significantly lower than AL rats. In contrast, in perfused hippocampus, IGF-I levels do not differ between CR and AL rats, but in both groups are significantly lower than in non-perfused hippocampus. *p < 0.001 non-perfused hippocampus CR compared AL; #p < 0.001 perfused AL and CR groups compared to non-perfused AL and CR groups.