Circulating Insulin-Like Growth Factor I Mediates Effects of Exercise on the Brain

Abstract

Physical exercise increases brain activity through mechanisms not yet known. We now report that in rats, running induces uptake of blood insulin-like growth factor I (IGF-I) by specific groups of neurons throughout the brain. Neurons accumulating IGF-I show increased spontaneous firing and a protracted increase in sensitivity to afferent stimulation. Furthermore, systemic injection of IGF-I mimicked the effects of exercise in the brain. Thus, brain uptake of IGF-I after either intracarotid injection or after exercise elicited the same pattern of neuronal accumulation of IGF-I, an identical widespread increase in neuronal c-Fos, and a similar stimulation of hippocampal brain-derived neurotrophic factor. When uptake of IGF-I by brain cells was blocked, the exercise-induced increase on c-Fos expression was also blocked. We conclude that serum IGF-I mediates activational effects of exercise in the brain. Thus, stimulation of the uptake of blood-borne IGF-I by nerve cells may lead to novel neuroprotective strategies.

Somatostatin and Alzheimer's disease

“…Our results demonstrate that peripheral administration of IGF-I increases cortical levels of this growth factor, as has been previously reported in other brain areas (Fernández et al, 1998;Carro et al, 2000). Indeed, peripheral IGF-I crosses the blood-brain barrier into the brain parenchyma (Reinhardt and Bondy 1994).…”

Clearance mechanisms of Alzheimer's amyloid-β peptide: implications for therapeutic design and diagnostic tests

“…Traditionally, IGF-1 has been attributed to mediating growth hormone activity, however evidence is now emerging linking IGF-1 with CNS development and repair, in particular, IGF-1 has been shown to play a role in neuroprotection and neurogenesis. 178,179 In addition, brain and serum levels of IGF-1 are reduced with age and reduced serum IGF-1 may be associated with increased risk for AD. 180,181 Carro et al in 2002 were the first to demonstrate that serum IGF-1 regulates brain Ab levels, an effect antagonized by tumour necrosis factor-a.…”

Acceleration of Visual System Development by Environmental Enrichment

“…Because it is known that BDNF expression strongly affects visual cortex development and plasticity (Huang et al, 1999), the effects of enriched environment that we documented on visual cortical development could be at least partially explained by BDNF precocious expression. However, it is known that enriched environment in the adult increases the expression of other factors that are potentially important for visual system development (neurotrophins, signal transduction molecules, NMDA receptors, GAD 65, CREB, and many others) (Molteni et al, 2002) and, in particular, increases IGF-I expression (Carro et al, 2000;Thoenen and Sendtner, 2002). IGF-I receptors are present in the occipital cortex (Frolich et al, 1998), and IGF-I could therefore influence the expression of molecules relevant for visual cortical plasticity such as nerve growth factor and BDNF itself.…”

“…Additional experiments should be performed to clarify which of these factors is causally involved in the effects of enriched environment on visual cortical development. In the adult, using different models of neurodegeneration, a causal relationship between the protective effects of exposure to enriched environment and the cascade from increased IGF-I to increased BDNF expression, has been demonstrated previously (Carro et al, 2000;Thoenen and Sendtner, 2002); it is not known whether this is true also for the developing brain.…”