Astragalus Polysaccharides Exerts A Neuroprotective Effect And Promotes IGF-1 Expression In A Rat Model Of Olivo-cerebellar Degeneration

The insulin-like growth factor-1 (IGF-1) is a pleiotropic trophic factor with a wide spectrum of actions on different CNS and PNS tissues. This trophic factor is selectively localized in the brain and mediates its physiological responses by interacting with transmembrane cell surface IGF-1 receptor. The activation of IGF-1 receptors stimulate cell growth, proliferation and differentiation, in addition to activation of glucose transport and prevention from cell death. Recent evidence indicates that intracellular IGF-1 signaling may be compromised in several neurodegenerative diseases. IGF-1 signaling disturbance has long been considered a cause of a small group of neurodegenerative diseases. Compromised IGF-1 support to neurons emerges as part of thepathological cascade during the degenerative process and contributes to neuronal demise in the majority of neurodegenerative diseases. Changes in the levels of IGF-1, a trophic hormone with multiple neuroprotective actions,have recently been observed in several human neurodegenerative illnesses. Therefor , IGF-1 has gained increasing attention for the treatment of neurodegenerative disorders.Astragalus membranaceus(AM) , the dry roots of Astragalus membranaceus (Fisch.) Bge.(Leguminosae), known as Huangqi in China, is the most important tonic in the traditional Chinese medicine. Astragalus polysaccharides (APS) are one of the main efficacious principles of Radix Astragali (Astragalus membranaceus), which is reported to have antioxidant, anti-diabetic and immunomodulatory activities. It had been reported that APS promotes the IGF-1 expression in nephrotic rats.However, to our knowledge , the promotion effect of APS on IGF-1 expression in the rat model of olivo - cerebellar degeneration has not yet been reported.In present study, we first analysed the motor performance of 3AP-treated rats in the inclined plane task.Treatment with AM or APS restored motor function in rats with neurotoxin-induced cerebellar deafferentation , restored the morphology change of inferior olive(10) neurons. When treated with AM or APS, 10 neurons , the targets of the neurotoxin, were rescued greatly, and the morphology change of 10 neurons was recovered distinctly. Then, we analysed mechanisms whereby APS restores motor function in rats with damage of the olivo-cerebellar pathway. Treatment with APS normalized calbindin in the cerebellum, which was depressed after 3AP-induced degeneration . Furthermore,APS promoted the expression of IGF-1 in the cerebellum in addition to increase serum IGF-1 level in the rat model of olivo-cerebellar degeneration.Altogether, these results indicate that AM or APS exerts neuroprotective effect in the olivo-cerebellar pathway: (1) treatment with AM or APS could increase the survival of 10 neurons greatly, and promote functional recovery. (2) AM and APS both could increase the serumlevel of IGF-1 in a dose-dependent manner. (3) APS could upregulate the expression of IGF-1 in the cerebellum.The results from our study together with its known low toxicity make it possible that APS might present potential effect as a treatment for neurodegenerative disease therapy.