Abstract
Neuritin is a new neurotropic factor implicated in nervous system development and plasticity. Studies have shown that Neuritin is upregulated in injured nerves, suggesting that it is involved in nerve repair. To test this hypothesis, we investigated whether recombinant human Neuritin could restore nerve structure and function in a rat model of sciatic nerve injury. Neuritin treatment had a dose-dependent effect on functional recovery 4 weeks after injury, as determined by the walking-track test. Similar trends were observed for gastrocnemius muscular strength and nerve conduction velocity. Additionally, sciatic nerve fiber density and organization as well as degree of remyelination were increased, while growth-associated protein 43 and neurofilament 200 expression was upregulated upon treatment with Neuritin. These findings demonstrate that Neuritin stimulates nerve regeneration and functional recovery and thus promotes the repair of injured sciatic nerves.
Highlights
Neurotrophic factors supported the migration, growth, and survival of neurons
Soluble recombinant hNeuritin was collected by linear elution by monitoring the major protein absorption peaks when flows through a HisTrap column packed with Ni Sepharose 6 Fast Flow Crude (Figure 1B)
Western blot analysis using an anti-His monoclonal antibody confirmed the identity of the protein as recombinant hNeuritin, which had a molecular weight of ∼11 kDa (Figure 1D), as confirmed by Coomassie staining
Summary
Neurotrophic factors supported the migration, growth, and survival of neurons. These secreted factors are critical for the maintenance and plasticity of the adult nervous system and are of clinical interest since they can serve as therapeutic agents in the treatment of neurodegenerative disorders and nerve injury (Vilar and Mira, 2016). Neuritin is upregulated in adult neural structures, such as the olfactory bulb, hippocampus, visual cortex, and Purkinje fibers (Nedivi et al, 1996, 2001; Yamagata et al, 1998) as well as during transient global ischemia, traumatic brain injury, spinal cord injury, and androgen treatment (Di Giovanni et al, 2005b; Han et al, 2007; Fargo et al, 2008; He et al, 2013) The latter was shown to promote functional recovery of injured facial nerves, which was associated with Neuritin upregulation; blocking androgen reduced Neuritin expression, suggesting a correlation between Neuritin, and functional recovery of injured facial nerves (Fargo et al, 2008)
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