1. Academic Validation
  2. The melanocortin ACTH 1-39 promotes protection of oligodendrocytes by astroglia

The melanocortin ACTH 1-39 promotes protection of oligodendrocytes by astroglia

  • J Neurol Sci. 2016 Mar 15;362:21-6. doi: 10.1016/j.jns.2016.01.009.
Robert P Lisak 1 Liljana Nedelkoska 1 Joyce A Benjamins 2
Affiliations

Affiliations

  • 1 Department of Neurology, Wayne State University School of Medicine, 3122 Elliman Building, 421 E. Canfield Ave., Detroit, MI 48201, United States.
  • 2 Department of Neurology, Wayne State University School of Medicine, 3122 Elliman Building, 421 E. Canfield Ave., Detroit, MI 48201, United States. Electronic address: jbenjami@med.wayne.edu.
Abstract

Damage to myelin and oligodendroglia (OL) in multiple sclerosis (MS) results from a wide array of mechanisms including excitotoxicity, neuroinflammation and oxidative stress. We previously showed that ACTH 1-39, a melanocortin, protects OL in mixed glial cultures and enriched OL cultures, inhibiting OL death induced by staurosporine, ionotropic glutamate receptors, quinolinic acid or Reactive Oxygen Species (ROS), but not nitric oxide (NO) or kynurenic acid. OL express Melanocortin Receptor 4 (MC4R), suggesting a direct protective effect of ACTH 1-39 on OL. However, these results do not rule out the possibility that astroglia (AS) or microglia (MG) also play roles in protection. To investigate this possibility, we prepared conditioned medium (CM) from AS and MG treated with ACTH, then assessed the protective effects of the CM on OL. CM from AS treated with ACTH protected OL from glutamate, NMDA, AMPA, quinolinic acid and ROS but not from kainate, staurosporine, NO or kynurenic acid. CM from MG treated with ACTH did not protect from any of these molecules, nor did CM from AS or MG not treated with ACTH. While protection of OL by ACTH from several toxic molecules involves direct effects on OL, ACTH can also stimulate AS to produce mediators that protect against some molecules but not Others. Thus the cellular mechanisms underlying the protective effects of ACTH for OL are complex, varying with the toxic molecules.

Keywords

Astroglia; Conditioned medium; Excitotoxicity; Inflammation; Melanocortin receptors; Multiple sclerosis; Oligodendroglia; Protection; Reactive oxygen species.

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