Pioglitazone promotes peripheral nerve remyelination after crush injury through CD36 upregulation.
In our previous study, we found that CD36-deficient mice showed significant delays in peripheral nerve remyelination after sciatic nerve crush injury and suggested that CD36 played an important role in the restoration of injured peripheral nerves. The aim of this study was to investigate whether CD36 upregulation can promote peripheral nerve remyelination. We made crush injury that caused demyelination and mild axonal degeneration to sciatic nerves and investigated the effect of pioglitazone (PIO) on the remyelination post-injury in C57Bl/6 wild-type and CD36-deficient mice. The immunohistochemistry with anti-CD36 antibody showed that CD36 was upregulated in macrophages infiltrating peripheral nerves from the wild-type mice by PIO administration at 1 week post-injury. The lectin histochemistry represented that infiltrating macrophages lessened in the wild-type mice at 3 weeks post-injury by PIO administration. General histopathology and morphometry indicated that thinly myelinated fibers and naked axons diminished in PIO-treated wild-type mice compared with non-treated wild-type mice at 3 weeks post-injury. No significant differences were observed in remyelination and number of infiltrating macrophages between PIO-treated and non-treated CD36-deficient mice. These results indicate that PIO promotes peripheral nerve remyelination possibly through CD36. It may be possible to apply PIO to the remedy against demyelinating neuropathies.
Department of Neurology, Osaka University Graduate School of Medicine, Osaka, Japan. etoh@neurol.med.osaka-u.ac.jp
Masaki
M
Eto
Hisae
H
Sumi
Harutoshi
H
Fujimura
Hiroo
H
Yoshikawa
Saburo
S
Sakoda
D000818:Animals; D018955:CD36 Antigens / Q000187:drug effects* / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009186:Myelin Sheath / Q000187:drug effects*; D009409:Nerve Crush; D018696:Neuroprotective Agents / Q000494:pharmacology*; D000077205:Pioglitazone; D012584:Sciatic Nerve / Q000187:drug effects* / Q000293:injuries / Q000473:pathology; D045162:Thiazolidinediones / Q000494:pharmacology*; D015854:Up-Regulation
D018955:CD36 Antigens; D018696:Neuroprotective Agents; D045162:Thiazolidinediones; D000077205:Pioglitazone