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

摘要: Increasing evidence indicates that circulating insulin-like growth factor I (IGF-I) acts as a peripheral neuroactive signal participating not only in protection against injury but also normal brain function. Epidemiological studies humans well recent experimental animals suggest blood-borne IGF-I may be involved cognitive performance. In agreement with observations humans, we found mice low-serum levels due to liver-specific targeted disruption of the gene presented deficits, evidenced by impaired performance hippocampal-dependent spatial-recognition task. Mice serum deficiency have disrupted long-term potentiation (LTP) hippocampus, cortex. Impaired hippocampal LTP was associated reduction density glutamatergic boutons led an imbalance glutamatergic/GABAergic synapse ratio this area. Behavioral and synaptic deficits were ameliorated IGF-I-deficient prolonged systemic administration normalized hippocampus. Altogether these results indicate liver-derived affects crucial aspects mature function; is, learning plasticity, through its trophic effects on central synapses. Declining during aging therefore contribute age-associated loss.