Phosphatidylinositol 3-kinase activity in murine motoneuron disease: the progressive motor neuropathy mouse

Neuroscience
R WageyC Krieger

Abstract

A murine model of motoneuron disease, the pmn/pmn mouse, shows a reduction in the retrograde transport of fluorescent probes applied directly onto the cut end of sciatic nerve. Brain-derived neurotrophic factor (BDNF), when co-applied with fluorescent tracers, increases the number of retrograde labelled motoneurons. We demonstrate here that spinal cord tissue from pmn/pmn mice had significantly reduced phosphatidylinositol 3-kinase activity and expression in the particulate fraction compared to controls, without changes in the activities or expression of the downstream kinases, protein kinase B/Akt or Erk1. Systemic administration of BDNF augmented phosphatidylinositol 3-kinase specific activity in spinal cord tissue from pmn/pmn and control mice, with a greater elevation in the particulate fractions of pmn/pmn mice than in controls. We examined the effect of inhibitors of phosphatidylinositol 3-kinase and mitogen-activated protein kinase kinase on the retrograde labelling of motoneurons, 24h following the direct application of inhibitors and Fluorogold to the cut end of sciatic nerve in control and pmn/pmn mice (labelling index). The mitogen-activated protein kinase kinase inhibitor PD 98059 had no effect on the labelling inde...Continue Reading

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Citations

Oct 16, 2003·Trends in Pharmacological Sciences·Charles KriegerSteven Pelech
Feb 20, 2003·Brain Research. Molecular Brain Research·Fang Cai, Cinda J Helke
Aug 15, 2002·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Erin E Rodgers, Anne B Theibert
Jan 9, 2007·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Alexander K MurashovMichael R Van Scott
Mar 27, 2004·American Journal of Physiology. Cell Physiology·Alexander K MurashovDouglas A Weidner

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