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Finding molecular targets to reverse nerve degeneration associated with diabetic peripheral neuropathy (DPN)
Author(s) -
Voithofer Gabrielle Elizabeth,
Clark Jessica
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.09347
Subject(s) - peripheral neuropathy , degeneration (medical) , dexamethasone , medicine , peripheral nervous system , zebrafish , diabetes mellitus , endocrinology , anatomy , chemistry , pathology , central nervous system , biochemistry , gene
One of the most common comorbidities associated with diabetes mellitus is diabetic peripheral neuropathy (DPN), which is the progressive degeneration of peripheral nerves. The manner in which DPN develops and the underlying mechanisms of peripheral nerve degeneration are currently unknown. Our lab has characterized a glucose‐induced model of DPN in zebrafish ( Danio rerio ) in which we observe defasciculation/degeneration of motor axons, decreased myelination, and a decrease in ensheathment by perineurial glia. Currently, we are interested in characterizing the molecular pathways involved in the degeneration we observe. To accomplish this, we are testing dexamethasone, a FDA‐characterized small molecule drug, in an effort to decrease the degree of nerve degeneration present after DPN onset. Beginning 5 days post fertilization (dpf) experimental larvae were immersed in 120 mM d ‐glucose for 7 seven days to induce DPN. At 10 dpf, larvae were additionally incubated with 0.5% dimethyl sulfoxide (DMSO) and a 1:1000 dilution of dexamethasone. As a control, a group of larvae were exposed to the same conditions without the addition of the drug treatment. Tg(nkx2.2a:meGFP) fish were used to allow visualization of perineurial glia 12 dpf using EVOS fluorescent microscopy. The percentage of motor axons ensheathed by perineurial glia was measured and quantified using FIJI. An increase in motor axons ensheathed by perineurial glia was apparent, furthermore the number of perineurial cells surrounding the motor axons appeared to increase as well. This increase in perineurial glia is meaningful because these cells form the blood‐nerve‐barrier, have phagocytic capabilities, and have also been shown to provide guidance cues for axonal regrowth. Future work will focus on characterizing the pathways affected by dexamethasone to uncover the molecular mechanisms potentially responsible for facilitating nerve regeneration after DPN onset. Support or Funding Information Support was provided by the Henson School of Science and Technology at Salisbury University.