Insulin-like growth factor-I and its receptor in the frontal cortex, hippocampus, and cerebellum of normal human and Alzheimer disease brains

Abstract

Assimilated evidence indicates that the neurotoxic potential of amyloid β (Aβ) peptide and an alteration in the level of growth factor(s) may possibly be involved in the loss of neurons observed in the brain of patients suffering from Alzheimer disease (AD), the prevalent cause of dementia in the elderly. In the present study, using receptor binding assays and immunocytochemistry, we evaluated the pharmacological profile of insulin‐like growth factor‐I (IGF‐I) receptors and the distribution of IGF‐I immunoreactivity in the frontal cortex, hippocampus, and cerebellum of AD and age‐matched control brains. In control brains, [125I]IGF‐I binding was inhibited more potently by IGF‐I than by Des(1‐3)IGF‐I, IGF‐II or insulin. The IC50 values for IGF‐I in the frontal cortex, hippocampus, and cerebellum of the normal brain did not differ significantly from the corresponding regions of the AD brain. Additionally, neither KD nor Bmax values were found to differ in the hippocampus of AD brains from the controls. At the regional levels, [125I]IGF‐I binding sites in the AD brain also remained unaltered compared to the controls. As for the peptide itself, IGF‐I immunoreactivity, in normal control brains, was evident primarily in a subpopulation of astrocytes in the frontal cortex and hippocampus, and in certain Purkinje cells of the cerebellum. In AD brains, a subset of Aβ‐containing neuritic plaques, apart from astrocytes, exhibit IGF‐I immunoreactivity. These results, taken together, suggest a role for IGF‐I in compensatory plasticity and/or survival of the susceptible neurons in AD brains. Synapse 38:450–459, 2000. © 2000 Wiley‐Liss, Inc.

Ovariectomy and gonadal hormone treatment: effects on insulin-like growth factor-1 receptors in the rat brain

“…However, in addition, binding to IGF-binding proteins (IGF-BP) cannot be ruled out. Previous studies [21,22] using 125 I-IGF-I autoradiography as well as competition studies concluded that the binding of 125 I-IGF-I observed was mainly due to binding to IGF-I receptors and not IGF-BP. Thus, it could be suggested that the increase in the 125 I-IGF-I binding observed in our study after estradiol and progesterone treatment is due to binding to IGF-I receptors.…”

Single Transmembrane Domain Insulin-Like Growth Factor-II/Mannose-6-Phosphate Receptor Regulates Central Cholinergic Function by Activating a G-Protein-Sensitive, Protein Kinase C-Dependent Pathway

“…Animals were killed by decapitation, and their brains were processed for either membrane binding assay or receptor autoradiography as described previously (Jafferali et al, 2000 125 I]insulin at 4°C for 6 h in 10 mM HEPES containing 0.5% BSA, 0.025% Bacitracin, 0.0125% N-ethylmaleimide (NEM), and 100 kIU/ml aprotinin. For each radioligand, competition binding was performed in the presence of 10 Ϫ6 to 10 Ϫ12 M IGF-I, IGF-II, Leu 27 IGF-II, and insulin.…”

Increased Activity and Altered Subcellular Distribution of Lysosomal Enzymes Determine Neuronal Vulnerability in Niemann-Pick Type C1-Deficient Mice

“…45,46 For the enzyme-linked procedure, 40-m sections were washed in PBS, treated with 1% hydrogen peroxide for 30 minutes, and then incubated overnight at room temperature with rabbit anti-IGF-II/M6P receptor (1:3000), goat anti-cathepsin D (1:200), or goatanti-cathepsin B (1:200) antiserum. Sections were then washed with PBS, exposed to horseradish peroxidaseconjugated secondary antibodies for 1 hour, and developed using the glucose oxidase-nickel enhancement method.…”