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Neurogenesis of corticospinal motor neurons extending spinal projections in adult mice

Department of Neurosurgery and Program in Neuroscience, Massachusetts General Hospital-Harvard Medical School Center for Nervous System Repair, Harvard Medical School, Massachusetts General Hospital, Boston, MA 02114, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.81). 12/2004; 101(46):16357-62. DOI: 10.1073/pnas.0406795101
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ABSTRACT The adult mammalian CNS shows a very limited capacity to regenerate after injury. However, endogenous precursors, or stem cells, provide a potential source of new neurons in the adult brain. Here, we induce the birth of new corticospinal motor neurons (CSMN), the CNS neurons that die in motor neuron degenerative diseases, including amyotrophic lateral sclerosis, and that cause loss of motor function in spinal cord injury. We induced synchronous apoptotic degeneration of CSMN and examined the fates of newborn cells arising from endogenous precursors, using markers for DNA replication, neuroblast migration, and progressive neuronal differentiation, combined with retrograde labeling from the spinal cord. We observed neuroblasts entering the neocortex and progressively differentiating into mature pyramidal neurons in cortical layer V. We found 20-30 new neurons per mm(3) in experimental mice vs. 0 in controls. A subset of these newborn neurons projected axons into the spinal cord and survived >56 weeks. These results demonstrate that endogenous precursors can differentiate into even highly complex long-projection CSMN in the adult mammalian brain and send new projections to spinal cord targets, suggesting that molecular manipulation of endogenous neural precursors in situ may offer future therapeutic possibilities for motor neuron degenerative disease and spinal cord injury.

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    • "As additional data emerge from clinical trials, it will be important to evaluate what subsets of patients might specifically benefit from cell therapy. The integrity of critical white matter tracts, such as corticospinal tracts, may dictate maximal recovery potential, providing a better predictor of outcome than baseline neurological exam after stroke (Chen et al., 2004; Stinear and Byblow, 2014). The role of physical rehabilitation in accelerating this recovery, or potentially even raising the ultimate predicted plateau remains under active investigation . "
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    • " Silver , 2008 ; Hoehn et al . , 2005 ; Rasmussen et al . , 2011 ; Sofroniew , 2009 ) . However , both positive and negative effects on neurogenesis and repair have been reported ( Ekdahl et al . , 2009 ) . Neurogenesis and survival of new neurons is increased following apoptotic neuronal ablation that does not result in an inflammatory response ( Chen et al . , 2004 ; Magavi et al . , 2000 ) . In contrast , microglial accumulation following stroke can promote neurogenesis and subsequent neuronal survival ( Thored et al . , 2009 ) . A recent study in zebrafish suggests that the inflammatory response is required to initiate neuro - genic proliferation in the adult VZ through pathways that are distinc"
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