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

Lisak, Robert P.; Nedelkoska, Liljana; Benjamins, Joyce A.

doi:10.1016/j.jns.2016.01.009

Cited by 6 publications

(4 citation statements)

References 49 publications

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“…As with the mixed glial cell cultures, OL in purified cultures were not protected from kynurenic acid or NO. Conditioned medium from astrocytes treated with ACTH was able to protect purified OL from glutamate, AMPA, quinolinic acid, and ROS but not from kainate, staurosporine, kynurenic acid or NO [ 98 ]. Thus, astrocytes may contribute to protection of OL from some but not all toxic molecules.…”

Section: Effects On Endogenous Cells Of the Cns With Potential Promentioning

confidence: 99%

Melanocortins, Melanocortin Receptors and Multiple Sclerosis

Lisak

Benjamins

2017

Brain Sciences

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The melanocortins and their receptors have been extensively investigated for their roles in the hypothalamo-pituitary-adrenal axis, but to a lesser extent in immune cells and in the nervous system outside the hypothalamic axis. This review discusses corticosteroid dependent and independent effects of melanocortins on the peripheral immune system, central nervous system (CNS) effects mediated through neuronal regulation of immune system function, and direct effects on endogenous cells in the CNS. We have focused on the expression and function of melanocortin receptors in oligodendroglia (OL), the myelin producing cells of the CNS, with the goal of identifying new therapeutic approaches to decrease CNS damage in multiple sclerosis as well as to promote repair. It is clear that melanocortin signaling through their receptors in the CNS has potential for neuroprotection and repair in diseases like MS. Effects of melanocortins on the immune system by direct effects on the circulating cells (lymphocytes and monocytes) and by signaling through CNS cells in regions lacking a mature blood brain barrier are clear. However, additional studies are needed to develop highly effective MCR targeted therapies that directly affect endogenous cells of the CNS, particularly OL, their progenitors and neurons.

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Section: Effects On Endogenous Cells Of the Cns With Potential Promentioning

confidence: 99%

Melanocortins, Melanocortin Receptors and Multiple Sclerosis

Lisak

Benjamins

2017

Brain Sciences

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“…We previously showed that ACTH was equally protective of OL in both mixed glial cultures and cultures highly enriched in OL. Since both astroglia and microglia are present at low levels, even in the highly enriched cultures, and both express MC4R (Caruso et al, ; Carniglia et al, ), we investigated whether OL protection by ACTH could be indirect, via effects of ACTH on astroglia or microglia (Lisak et al, ). We found that ACTH can stimulate astroglia in culture to produce mediators that protect OL against some toxic molecules, but not others.…”

Section: Discussionmentioning

confidence: 99%

“…Cultures enriched in mature OL were prepared from forebrains of Sprague Dawley neonatal rats (Charles River Laboratories) without regard to sex, using our previous modifications (Boullerne et al, 2001; Lisak et al, ) of the “shake‐off” method of McCarthy and DeVellis (1980). For cultures highly enriched in OL (Lisak et al, ), the glial bed layers were subjected to shake off from the astroglial bed layer every 5–7 days. Cells from the 3 rd , 4 th or 5 th shake offs were plated on plastic dishes for one hour, and the unattached cells were re‐plated for an additional hour to remove more microglia.…”

Section: Methodsmentioning

confidence: 99%

Melanocortin receptor subtypes are expressed on cells in the oligodendroglial lineage and signal ACTH protection

Benjamins

Nedelkoska

Lisak

2017

J of Neuroscience Research

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ACTH, a melanocortin peptide used to treat multiple sclerosis (MS) relapses, acts by stimulating adrenal corticosteroid (CS) production via melanocortin receptor 2 (MC2R), but it may also exert a therapeutic effect independent of CS by stimulating other melanocortin receptors (MCR) distributed in many tissues, including the brain. We reported that oligodendroglia (OL) and oligodendroglial precursor cells (OPC) express MC4R, and that ACTH 1-39 protects OL and OPC in vitro from cell death induced by mechanisms likely involved in white matter damage in MS. This study investigates expression of MC1R, MC2R, MC3R and MC5R in OL and MC4R in OPC using immunocytochemistry with MCR subtype specific antibodies. OL express surface MC1R, MC3R and MC5R, in addition to MC4R. To investigate whether these receptors are functional, we asked if signaling through MCR is involved in ACTH protection of cultured rat OL from apoptosis (staurosporine), or cell death induced by excitotoxicity (glutamate), reactive oxygen species (ROS), or an inflammatory mediator (quinolinic acid). Like ACTH 1-39, MCR subtype specific agonists for MC1R, MC3R, MC4R and MC5R all protected OL from these insults. Conversely, antagonists for MC3R and MC4R blocked ACTH protection of OL. We then investigated the role of MC4R, as a prototype MCR, in protection and proliferation of OPC; MC4R agonists protected OPC and increased their proliferation, while antagonists blocked these effects. Our results demonstrate that MCR on OL and OPC are functional and activate signaling pathways that protect against mechanisms involved in OL damage in MS, suggesting potential beneficial effects in neurologic diseases.

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“…MC4R activation displays neuroprotective and neuroregenerative effects in several models of animal neurodegenerative diseases ( 102 ). ACTH has been found to promote oligodendrocyte protection ( 103 ) and neuron protection from inflammatory, excitotoxic, and apoptotic damages ( 104 , 105 ). Dated research showed that rat embryo neurons respond to ACTH displaying a denser neuritic network ( 106 ) and displayed neuroprotective effects after hemorrhage insult by activating anti-inflammatory pathways ( 107 , 108 ).…”

Section: Extra-adrenal Effects Of Acthmentioning

confidence: 99%

Non-Canonical Effects of ACTH: Insights Into Adrenal Insufficiency

et al. 2021

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IntroductionAdrenocorticotropic hormone (ACTH) is produced from proopiomelanocortin, which is predominantly synthetized in the corticotroph and melanotroph cells of the anterior and intermediate lobes of the pituitary gland and the arcuate nucleus of the hypothalamus. Although ACTH clearly has an effect on adrenal homeostasis and maintenance of steroid hormone production, it also has extra-adrenal effects that require further elucidation.MethodsWe comprehensively reviewed English language articles, regardless of whether they reported the presence or absence of adrenal and extra-adrenal ACTH effects.ResultsIn the present review, we provide an overview on the current knowledge on adrenal and extra-adrenal effects of ACTH. In the section on adrenal ACTH effects, we focused on corticosteroid rhythmicity and effects on steroidogenesis, mineralocorticoids and adrenal growth. In the section on extra-adrenal effects, we have analyzed the effects of ACTH on the osteoarticular and reproductive systems, adipocytes, immune system, brain and skin. Finally, we focused on adrenal insufficiency.ConclusionsThe role of ACTH in maintaining the function of the hypothalamic–pituitary–adrenal axis is well known. Conversely, if we broaden our vision and analyze its role as a potential treatment strategy in other conditions, it will be evident in the literature that researchers seem to have abandoned this aspect in studies conducted several years ago. We believe it is worth re-evaluating the role of ACTH considering its noncanonical effects on the adrenal gland itself and on extra-adrenal organs and tissues; however, this would not have been possible without the recent advances in the pertinent technologies.

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

Cited by 6 publications

References 49 publications

Melanocortins, Melanocortin Receptors and Multiple Sclerosis

Melanocortins, Melanocortin Receptors and Multiple Sclerosis

Melanocortin receptor subtypes are expressed on cells in the oligodendroglial lineage and signal ACTH protection

Non-Canonical Effects of ACTH: Insights Into Adrenal Insufficiency

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