Induction of endogenous neural precursors in mouse models of spinal cord injury and disease.
Adult neural precursor cells (NPCs) in the mammalian central nervous system (CNS) have been demonstrated to be responsive to conditions of injury and disease. Here we investigated the response of NPCs in mouse models of spinal cord disease [motor neuron disease (MND)] with and without sciatic nerve axotomy, and spinal cord injury (SCI). We found that neither axotomy, nor MND alone brought about a response by Nestin-positive NPCs. However, the combination of the two resulted in mobilization of NPCs in the spinal cord. We also found that there was an increase in the number of NPCs following SCI which was further enhanced by systemic administration of the neuregulatory cytokine, leukaemia inhibitory factor (LIF). NPCs were demonstrated to differentiate into astrocytes in axotomized MND mice. However, significant differentiation into the various neural cell phenotypes was not demonstrated at 1 or 2 weeks following SCI. These data suggest that factors inherent to injury mechanisms are required for induction of an NPC response in the mammalian spinal cord.
Azari
M F
MF
Department of Anatomy and Cell Biology, Faculty of Medicine, Monash University, Clayton, Australia.
Profyris
C
C
Zang
D W
DW
Petratos
S
S
Cheema
S S
SS
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D019771:Axotomy / Q000379:methods; D002452:Cell Count / Q000379:methods; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D020287:In Situ Nick-End Labeling / Q000379:methods; D015850:Interleukin-6 / Q000494:pharmacology; D007381:Intermediate Filament Proteins / Q000378:metabolism; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D009474:Neurons / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism; D018121:Receptors, Cytokine / Q000378:metabolism; D053606:Receptors, OSM-LIF; D020426:Sciatic Neuropathy / Q000378:metabolism / Q000503:physiopathology; D013118:Spinal Cord Diseases / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D013234:Stem Cells / Q000187:drug effects / Q000502:physiology*; D013482:Superoxide Dismutase / Q000235:genetics
D005904:Glial Fibrillary Acidic Protein; D015850:Interleukin-6; D007381:Intermediate Filament Proteins; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; C507838:Lif protein, mouse; C507841:Lifr protein, mouse; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D018121:Receptors, Cytokine; D053606:Receptors, OSM-LIF; C109415:SOD1 G93A protein; D013482:Superoxide Dismutase; D020796:Receptor, Platelet-Derived Growth Factor alpha