Desert Hedgehog is a Mediator of Demyelination in Compression Neuropathies.

Desert Hedgehog is a Mediator of Demyelination in Compression Neuropathies. Exp Neurol. 2015 Apr 30; Authors: Jung J, Frump D, Su J, Wang W, Mozaffar T, Gupta R Abstract The secreted protein desert hedgehog (dhh) controls the formation of the nerve perineurium during development and is a key component of Schwann cells that ensures peripheral nerve survival. We postulated that dhh may play a critical role in maintaining myelination and investigated its role in demyelination induced compression neuropathies by using a post-natal model of a chronic nerve injury in wildtype and dhh(-/-) mice. We evaluated demyelination using electrophysiological, morphological, and molecular approaches. Dhh transcripts and protein are down-regulated early after injury in wild-type mice, suggesting an intimate relationship between the hedgehog pathway and demyelination. In dhh(-/-) mice, nerve injury induced more prominent and severe demyelination relative to their wild-type counterparts, suggesting a protective role of Dhh. Alterations in nerve fiber characteristics included significant decreases in nerve conduction velocity, increased myelin debris, and substantial decreases in internodal length. Furthermore, in vitro studies showed that dhh blockade via either adenovirus-mediated (shRNA) or pharmacological inhibition both resulted in severe demyelination, which could be rescued by exogenous Dhh. Exogenous Dhh was protective against this demyelination and maintained myelina...
Source: Experimental Neurology - Category: Neurology Authors: Tags: Exp Neurol Source Type: research

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