Pleiotrophin is a neurotrophic factor for spinal motor neurons

Abstract

Regeneration in the peripheral nervous system is poor after chronic denervation. Denervated Schwann cells act as a ''transient target'' by secreting growth factors to promote regeneration of axons but lose this ability with chronic denervation. We discovered that the mRNA for pleiotrophin (PTN) was highly up-regulated in acutely denervated distal sciatic nerves, but high levels of PTN mRNA were not maintained in chronically denervated nerves. PTN protected spinal motor neurons against chronic excitotoxic injury and caused increased outgrowth of motor axons out of the spinal cord explants and formation of ''miniventral rootlets.'' In neonatal mice, PTN protected the facial motor neurons against cell death induced by deprivation from target-derived growth factors. Similarly, PTN significantly enhanced regeneration of myelinated axons across a graft in the transected sciatic nerve of adult rats. Our findings suggest a neurotrophic role for PTN that may lead to previously unrecognized treatment options for motor neuron disease and motor axonal regeneration.anaplastic lymphoma kinase ͉ neurotrophism ͉ Schwann cell ͉ nerve regeneration ͉ denervation

Electrical Stimulation to Enhance Axon Regeneration After Peripheral Nerve Injuries in Animal Models and Humans

“…Examples include the upregulation of neurotrophic factors, galectin-1, and cytoskeletal proteins, including actin and T-α-1 tubulin in the neurons [43][44][45][46], and neurotrophic factors and their receptors in the Schwann cells ( Fig. 3a) [31,41,42,[47][48][49]. A specific example of upregulation of T-α-1 tubulin in the neurons is shown in Fig.…”

Stem cells for the replacement of inner ear neurons and hair cells

“…Repair of lesioned peripheral nerves can also be accomplished by the regeneration of motor and sensory neuronal processes (Brushart, 1993, Mi et al, 2007. Interactions with extracellular factors from glial cells as well the targets of the growing axon have been shown to have an influence on the regrowth of these processes and formation of new synapses (Fraher, 2000, Harel and Strittmatter, 2006, Hata et al, 2006, Pasterkamp and Verhaagen, 2006.…”

Intricate interplay between astrocytes and motor neurons in ALS

“…These genes were also among the most highly expressed genes in these glial cultures (Dataset S3). Other highly expressed injury/stress response-secreted genes that are down-regulated in MT glia include Sepp1, which has been implicated as an extracellular antioxidant, Apolipoprotein D, which is known to be transcriptionally up-regulated in response to and involved in mechanisms regulating protection from oxidative stress (30)(31)(32), and Pleiotrophin, which has been shown to be a trophic factor for spinal motor neurons, protecting against chronic excitotoxic injury and causing increased outgrowth of motor axons out of spinal cord explants (33).…”