Protective effects of insulin‐like growth factor‐I on the somatostatinergic system in the temporal cortex of β‐amyloid‐treated rats

Abstract

Insulin-like growth factor-I (IGF-I) has protective effects against b-amyloid (Ab)-induced neuronal cell death. Because alterations of the somatostatinergic system have been described in Alzheimer's disease, we investigated the effects of the Ab peptide and the possible protective role of IGF-I on the somatostatinergic system of the rat temporal cortex and on cell death and phosphorylated (p)-Akt levels in this area. Ab25-35 was administered intracerebroventricularly to male rats via an osmotic minipump over 14 days (300 pmol/day). Another group received a subcutaneous IGF-I infusion (50 lg/kg/day), concomitant with Ab25-35 administration, whereas a third group received IGF-I alone. Ab25-35 significantly decreased the somatostatin (SRIF)-like immunoreactive content and the SRIF receptor density, as a result of a decrease in the levels of the SRIF receptor subtype 2. The inhibitory effect of SRIF on adenylyl cyclase activity was significantly lower after Ab25-35 infusion, whereas the levels of the inhibitory G protein subunit Gia1, Gia2 or Gia3 were unaltered. Cell death was increased and p-Akt levels decreased in Ab25-35-treated animals. IGF-I administration increased immunoreactive IGF-I levels in the temporal cortex and restored all parameters affected by Ab25-35 to baseline values. These findings suggest that IGF-I prevents the deleterious effect of Ab25-35 on the somatostatinergic system.

Somatostatin and Alzheimer's disease

“…infusion of A1-40 or A25-35 for 14 days results in a significant reduction in SRIF-LI content in the rat hippocampus, frontoparietal cortex and temporal cortex (Nag et al, 1999;Hervás-Aguilar at al., 2005;Aguado-Llera et al, 2005;Burgos-Ramos et al, 2007), which parallels that seen in postmortem brains of patients with AD (Davies et al 1980). These findings suggest that the accumulation of A peptides contributes, at least partly, to the well-documented deficits in SRIF-LI content throughout the AD brain.…”

Growth factors and cytokines/chemokines as surrogate biomarkers in cerebrospinal fluid and blood for diagnosing Alzheimer’s disease and mild cognitive impairment

“…Platelet-derived growth factor (PDGF) has been found to upregulate amyloid-precursor-protein in hippocampus by inducing secretases (Gianni et al 2003;Zambrano et al 2004;Lim et al 2007). Insulin-like growth factor-I (IGF-I) regulates beta-amyloid levels and displays protective effects against beta-amyloid toxicity (Carro et al 2002;Aguado-Llera et al 2005). Fibroblast growth factor-2 (FGF-2) shares binding sites with beta-amyloid fibrils on heparan sulfate from cerebral cortex (Lindahl et al 1999) and plays a role in beta-amyloid toxicity (Cantara et al 2005).…”

Beta-amyloid toxicity and reversal in embryonic rat septal neurons

“…Protection against stroke is conferred by bFGF in rats [39] and FGF protects against Aβ toxicity in endothelial cells [7]. Rat temporal cortex is protected against Aβ by IGF1 [2]. In fact, IGF1 has so many protective functions its decline appears to be related to senescence in the brain [37].…”