Format

Send to

Choose Destination
Exp Neurol. 2015 Nov;273:161-7. doi: 10.1016/j.expneurol.2015.08.012. Epub 2015 Aug 20.

Melanocortin receptor agonist ACTH 1-39 protects rat forebrain neurons from apoptotic, excitotoxic and inflammation-related damage.

Author information

1
Department of Neurology, Wayne State University School of Medicine, 8D University Health Center, 4201 St. Antoine St., Detroit, MI 48201, USA. Electronic address: rlisak@med.wayne.edu.
2
Department of Neurology, Wayne State University School of Medicine, 8D University Health Center, 4201 St. Antoine St., Detroit, MI 48201, USA.

Abstract

Patients with relapsing-remitting multiple sclerosis (RRMS) are commonly treated with high doses of intravenous corticosteroids (CS). ACTH 1-39, a member of the melanocortin family, stimulates production of CS by the adrenals, but melanocortin receptors are also found in the central nervous system (CNS) and on immune cells. ACTH is produced within the CNS and may have direct protective effects on glia and neurons independent of CS. We previously reported that ACTH 1-39 protected oligodendroglia (OL) and their progenitors (OPC) from a panel of excitotoxic and inflammation-related agents. Neurons are the most vulnerable cells in the CNS. They are terminally differentiated, and sensitive to inflammatory and excitotoxic insults. For potential therapeutic protection of gray matter, it is important to investigate the direct effects of ACTH on neurons. Cultures highly enriched in neurons were isolated from 2-3 day old rat brain. After 4-7 days in culture, the neurons were treated for 24h with selected toxic agents with or without ACTH 1-39. ACTH 1-39 protected neurons from death induced by staurosporine, glutamate, NMDA, AMPA, kainate, quinolinic acid, reactive oxygen species and, to a modest extent, from rapidly released NO, but did not protect against kynurenic acid or slowly released nitric oxide. Our results show that ACTH 1-39 protects neurons in vitro from several apoptotic, excitotoxic and inflammation-related insults.

KEYWORDS:

ACTH; Amyotrophic lateral sclerosis; Corticosteroids; Glutamate; Melanocortin receptors; Multiple sclerosis; Neuroinflammation; Neurons; Protection

PMID:
26300474
DOI:
10.1016/j.expneurol.2015.08.012
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center