Role of plasminogen activator in spinal cord remodeling after spinal cord injury.
Plasminogen activators play an active role in synaptic plasticity associated with the crossed phrenic phenomenon (CPP) and recovery of respiratory function following spinal cord injury. A genetic approach has been used to identify molecular mechanisms underlying this synaptic plasticity. Knockout mice lacking different genes in the plasminogen activator/plasmin system demonstrate that expression of urokinase plasminogen activator (uPA) is required during the critical 1-2h delay period following C2-hemisection for the acquisition of a good CPP response. uPA knockout mice fail to show the structural remodeling of phrenic motorneuron synapses that underlie the CPP response. Potential mechanisms by which uPA may promote phrenic motorneuron synaptic plasticity have been explored. Expression of uPA receptors, uPAR and LRP-1, are both up-regulated in the ipsilateral phrenic motor nucleus (PMN) following C2-hemisection. A comparison of microarray data and real-time PCR analysis of mRNAs induced in the PMN after hemisection indicate potential cell signaling pathways downstream of uPA's interaction with these cell surface receptors in the PMN. Knowledge of these uPA-mediated signaling pathways may identify potential means for the pharmacological activation of the synaptic plasticity required for recovery of phrenic motorneuron activity.
Seeds
Nicholas W
NW
Department of Biochemistry & Molecular Genetics and Neuroscience Program, University of Colorado School of Medicine, Aurora, CO 80045, United States. Nicholas.Seeds@ucdenver.edu
Akison
Lisa
L
Minor
Kenneth
K
D000818:Animals; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000235:genetics; D007839:Functional Laterality / Q000502:physiology; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009046:Motor Neurons / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D010791:Phrenic Nerve / Q000293:injuries / Q000502:physiology; D010960:Plasminogen Activators / Q000235:genetics / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator / Q000172:deficiency; D020127:Recovery of Function / Q000502:physiology*; D015656:Respiratory Mechanics / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology
D055293:Receptors, Urokinase Plasminogen Activator; D010960:Plasminogen Activators