Insulin-like growth factor 1 reduces age-related disorders induced by prenatal stress in female rats

Stress during the prenatal period can induce permanent abnormalities in adult life such as increased anxiety-like behavior and hyperactivity of hypothalamo-pituitary-adrenal (HPA) axis system. The present study was designed to investigate whether prenatal stress could induce spatial learning impairment in aged female rats. Furthermore, since it has been recently reported that insulin-like growth factor 1 (IGF-1) attenuates spatial learning deficits in aged rats and promotes neurogenesis in the hippocampus, we assessed the impact of a chronic infusion of IGF-1 on age-related disorders. Our results show that females stressed during prenatal life exhibit learning impairments in the water maze task. Chronic IGF-1 treatment restores their spatial abilities, reduces their HPA axis dysfunction and increases plasma estradiol levels. Parallel to these effects, chronic IGF-1 up-regulates neural proliferation in the dentate gyrus of the hippocampus. These findings support the hypothesis of an early programming of the vulnerability to some neurological diseases during senescence and reinforce the potential therapeutic interest of IGF-1 during brain aging. (C) 2005 Elsevier Inc. All rights reserved.