Endocrine, liver-derived IGF-I is of importance for spatial learning and memory in old mice

Abstract

IGF-I is a neuroprotective hormone, and neurodegenerative disorders, including Alzheimer's disease, have been associated with decreased serum IGF-I concentration. In this study, IGF-I production was inactivated in the liver of adult mice (LI-IGF-I / ), resulting in an approximately 80-85% reduction of circulating IGF-I concentrations. In young (6-month-old) mice there was no difference between the LI-IGF-I / and the control mice in spatial learning and memory as measured using the Morris water maze test. In old (aged 15 and 18 months) LI-IGF-I / mice, however, the acquisition of the spatial task was slower than in the controls. Furthermore, impaired spatial working as well as reference memory was observed in the old LI-IGF / mice. Histochemical analyses revealed an increase in dynorphin and enkephalin immunoreactivities but decreased mRNA levels in the hippocampus of old LI-IGF-I / mice. These mice also displayed astrocytosis and increased metabotropic glutamate receptor 7a-immunoreactivity. These neurochemical disturbances suggest synaptic dysfunction and early neurodegeneration in old LI-IGF-I / mice. The decline in serum IGF-I with increasing age may therefore be important for the age-related decline in memory function.

Skin and brain age together: The role of hormones in the ageing process

“…In another important study, endocrine, liver-derived IGF-I improved spatial learning and memory functions in old mice (Svensson et al, 2006).…”

Central actions of liver-derived insulin-like growth factor I underlying its pro-cognitive effects

“…15 Based on all this evidence, we recently proposed that serum IGF-I contributes to building a 'cognitive reserve', 16 a concept that refers to the availability of functional resources supporting cognition which was originally coined to explain relative resilience to dementia in relation to education level. 17 This purported role of serum IGF-I could help to explain its neuroprotective effects against diverse types of insults 18 and will theoretically support an active role of this circulating growth factor on higher brain functions.…”

Growth factors and glucose homeostasis in diabetic rats: effects of exercise training

“…These metabolic alterations may modify GH and IGF-1 synthesis and release. 7,8 Diabetes leads to a variety of complications that include nerve nephropathy, retinopathy, cardiovascular and nerve disease. 1,9 Several observations indicate that IGF-1 plays an important role in the development of central nervous system.…”