ACTH protects mature oligodendroglia from excitotoxic and inflammation-related damage in vitro

GLIA

Volumn 61, Issue 8, 2013, Pages 1206-1217

  Benjamins, Joyce A ^a   Nedelkoska, Liljana ^a   Bealmear, Beverly ^a   Lisak, Robert P ^a  

^a WAYNE STATE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Corticosteroids; Glutamate; Melanocortin receptors; Neuroinflammation; Protection

Indexed keywords

ALPHA AMINO 3 HYDROXY 5 METHYL 4 ISOXAZOLEPROPIONIC ACID; CORTICOTROPIN[1-39]; KAINIC ACID; KYNURENIC ACID; MELANOCORTIN 4 RECEPTOR; N METHYL DEXTRO ASPARTIC ACID; QUINOLINIC ACID; REACTIVE OXYGEN METABOLITE; STAUROSPORINE;

ANIMAL CELL; ARTICLE; ASTROCYTE; CONCENTRATION (PARAMETERS); CONCENTRATION RESPONSE; CONTROLLED STUDY; CYTOTOXICITY TEST; EXCITOTOXICITY; GLIA CELL; INCUBATION TIME; MACROGLIA; METABOLITE; MICROGLIA; NERVE CELL NECROSIS; NERVOUS SYSTEM INFLAMMATION; NEUROPROTECTION; NONHUMAN; OLIGODENDROGLIA; PRIORITY JOURNAL; PROTEIN EXPRESSION; RAT;

CORTICOSTEROIDS; GLUTAMATE; MELANOCORTIN RECEPTORS; NEUROINFLAMMATION; PROTECTION;

ADRENOCORTICOTROPIC HORMONE; ANIMALS; ANIMALS, NEWBORN; APOPTOSIS; CELLS, CULTURED; GLUTAMIC ACID; INFLAMMATION; NEUROPROTECTIVE AGENTS; OLIGODENDROGLIA; RATS; REACTIVE OXYGEN SPECIES;

EID: 84880701515     PISSN: 08941491     EISSN: 10981136     Source Type: Journal    
DOI: 10.1002/glia.22504     Document Type: Article

References (99)

1. Arranz AM, Hussein A, Alix JJ, Pérez-Cerdá F, Allcock N, Matute C, Fern R. 2008. Functional glutamate transport in rodent optic nerve axons and glia. Glia 56:1353-1367.
2. Arya R, Shinnar S, Glauser TA. 2012. Corticosteroids for the treatment of infantile spasms: A systematic review. J Child Neurol 27:1284-1288.
3. Bakiri Y, Burzomato V, Frugier G, Hamilton NB, Káradóttir R, Attwell D. 2003. Glutamatergic signaling in the brain's white matter. Neuroscience 158:266-274.
4. Bakiri Y, Hamilton NB, Káradóttir R, Attwell D. 2008. Testing NMDA receptor block as a therapeutic strategy for reducing ischaemic damage to CNS white matter. Glia 56:233-240.
5. Bansal R, Stefansson K, Pfeiffer SE. 1992. Proligodendroblast antigen (POA), a developmental antigen expressed by A007/O4-positive oligodendrocyte progenitors prior to the appearance of sulfatide and galactocerebroside. J Neurochem 58:2221-2229.
6. Baram TZ, Mitchell WG, Tournay A, Snead OC, Hanson RA, Horton EJ. 1996. High-dose corticotropin (ACTH) versus prednisone for infantile spasms: A prospective, randomized, blinded study. Pediatrics 97:375-379.
7. Barnes MP, Bateman DE, Cleland PG, Dick DJ, Walls TJ, Newman PK, Saunders M, Tilley PJ. 1985. Intravenous methylprednisolone for multiple sclerosis in relapse. J Neurol Neurosurg Psychiatry 48:157-159.
8. Barnes D, Hughes RA, Morris RW, Wade-Jones O, Brown P, Britton T, Francis DA, Perkin GD, Rudge P, Swash M, Katifi H, Farmer S, Frankel J. 1997. Randomised trial of oral and intravenous methylprednisolone in acute relapses of multiple sclerosis. Lancet 349:902-906.
9. Benjamins JA, Nedelkoska L. 2007. Cyclic GMP- dependent pathways protect differentiated oligodendrocytes from multiple types of injury. Neurochem Res 32:321-329.
10. Benjamins JA, Nedelkoska L, Lisak RP, Hannigan JH, Sokol RJ. 2011. Cytokines reduce toxic effects of ethanol on oligodendroglia. Neurochem Res 36:1677-1686.
11. Bertolini A, Tacchi R, Vergoni AV. 2009. Brain effects of melanocortins. Pharmacol Res 59:13-47.
12. Bertrand R, Solary E, O'Connor P, Kohn KW, Pommier Y. 1994. Induction of a common pathway of apoptosis by staurosporine. Exp Cell Res 211:314-321.
13. Bottenstein JE. 1986. Growth requirements in vitro of oligodendrocyte cell lines and neonatal rat brain oligodendrocytes. Proc Natl Acad Sci U S A 83:1955-1959.
14. Boullerne AI, Benjamins JA. 2006. Nitric oxide synthase expression and nitric oxide toxicity in oligodendrocytes. Antioxid Redox Signal 8:967-980.
15. Brod SA, Bauer V, Hood Z. Oral ACTH (H.P. Acthar(®)Gel) inhibits IL-1 and IL-17 secretion in humans. Biomed Pharmacother 2012;66:36-39.
16. Brod SA, Hood ZM. 2008. Ingested (oral) alpha-MSH inhibits acute EAE. J Neuroimmunol 193:106-112.
17. Brod SA, Hood ZM. 2011. Ingested (oral) ACTH inhibits EAE. J Neuroimmunol 232:131-135.
18. Burzomato V, Frugier G, Pérez-Otaño I, Kittler JT, Attwell D. 2010. The receptor subunits generating NMDA receptor mediated currents in oligodendrocytes. J Physiol 588:3403-3414.
19. Butt AM. 2006. Neurotransmitter-mediated calcium signalling in oligodendrocyte physiology and pathology. Glia 54:666-675.
20. Cammer W. 2001. Oligodendrocyte killing by quinolinic acid in vitro. Brain Res 896:157-160.
21. Caruso C, Carniglia L, Durand D, Gonzalez PV, Scimonelli TN, Lasaga M. 2012. Melanocortin 4 receptor activation induces brain-derived neurotrophic factor expression in rat astrocytes through cyclic AMP-protein kinase A pathway. Mol Cell Endocrinol 348:47-54.
22. Caruso C, Durand D, Schiöth HB, Rey R, Seilicovich A, Lasaga M. 2007. Activation of melanocortin 4 receptors reduces the inflammatory response and prevents apoptosis induced by lipopolysaccharide and interferon-gamma in astrocytes. Endocrinology 148:4918-4926.
23. Catania A, Gatti S, Colombo G, Lipton JM. 2004. Targeting melanocortin receptors as a novel strategy to control inflammation. Pharmacol Rev 56:1-29.
24. Catania A, Lonati C, Sordi A, Carlin A, Leonardi P, Gatti S. 2010. The melanocortin system in control of inflammation. Sci World J 10:1840-1853.
25. Chachua T, Yum MS, Velíšková J, Velíšek L. 2011. Validation of the rat model of cryptogenic infantile spasms. Epilepsia 52:1666-1677.
26. Chiarugi A, Cozzi A, Ballerini C, Massacesi L, Moroni F. 2001. Kynurenine 3-mono-oxygenase activity and neurotoxic kynurenine metabolites increase in the spinal cord of rats with experimental allergic encephalomyelitis. Neuroscience 102:687-695.
27. Clarner T, Parabucki A, Beyer C, Kipp M. 2011. Corticosteroids impair remyelination in the corpus callosum of cuprizone-treated mice. J Neuroendocrinol 23:601-611.
28. De Biase LM, Bergles DE. 2011. Same players, different game: AMPA receptor regulation in oligodendrocyte progenitors. Nat Neurosci 26:1358-1360.
29. De Kloet ER, Joëls M, Holsboer F. 2005. Stress and the brain: From adaptation to disease. Nat Rev Neurosci 6:463-475.
30. De Kloet ER, Vreugdenhil E, Oitzl MS, Joëls M. 1998. Brain corticosteroid receptor balance in health and disease. Endocr Rev 19:269-301.
31. Delgado R, Carlin A, Airaghi L, Demitri MT, Meda L, Galimberti D, Baron P, Lipton JM, Catania A. 1998. Melanocortin peptides inhibit production of proinflammatory cytokines and nitric oxide by activated microglia. J Leukoc Biol 63:740-745.
32. Deng W, Wang H, Rosenberg PA, Volpe JJ, Jensen FE. 2004. Role of metabotropic glutamate receptors in oligodendrocyte excitotoxicity and oxidative stress. Proc Natl Acad Sci U S A 101:7751-7776.
33. DiNatale BC, Murray IA, Schroeder JC, Flaveny CA, Lahoti TS, Laurenzana EM, Omiecinski CJ, Perdew GH. 2010. Kynurenic acid is a potent endogenous aryl hydrocarbon receptor ligand that synergistically induces interleukin-6 in the presence of inflammatory signaling. Toxicol Sci 115:89-97.
34. Duckers HJ, Verhaagen J, de Bruijn E, Gispen WH. 1994. Effective use of a neurotrophic ACTH4-9 analogue in the treatment of a peripheral demyelinating syndrome (experimental allergic neuritis). An intervention study. Brain 117 (Pt 2):365-374.
35. Dyer CA, Benjamins JA. 1988. Redistribution and internalization of antibodies to galactocerebroside by oligodendroglia. J Neurosci 8:883-891.
36. Dyer CA, Benjamins JA. 1990. Glycolipids and transmembrane signaling: Antibodies to galactocerebroside cause an influx of calcium in oligodendrocytes. J Cell Biol 111:625-633.
37. Dyer JK, Ahmed AR, Oliver GW, Poulton CW, Haynes LW. 1993. Solubilisation partial characterisation of the alpha-MSH receptor on primary rat Schwann cells. FEBS Lett 336:103-106.
38. Dyer JK, Philipsen HL, Tonnaer JA, Hermkens PH, Haynes LW. 1995. Melanocortin analogue Org2766 binds to rat Schwann cells, upregulates NGF low-affinity receptor p75, and releases neurotrophic activity. Peptides 16:515-522.
39. Forslin-Aronsson A, Spulber S, Oprica M, Winblad B, Post C, Schultzberg M. 2007. Alpha-MSH rescues neurons from excitotoxic cell death. J Mol Neurosci 33:239-251.
40. Frigo M, Cogo MG, Fusco ML, Gardinetti M, Frigeni B. 2012. Glutamate and multiple sclerosis. Curr Med Chem 19:1295-1299.
41. Galimberti D, Baron P, Meda L, Prat E, Scarpini E, Delgado R, Catania A, Lipton JM, Scarlato G. 1999. Alpha-MSH peptides inhibit production of nitric oxide and tumor necrosis factor-alpha by microglial cells activated with beta-amyloid and interferon gamma. Biochem Biophys Res Commun 263:251-256.
42. Geurts JJ, Wolswijk G, Bö L, van der Valk P, Polman CH, Troost D, Aronica E. 2003. Altered expression patterns of group I and II metabotropic glutamate receptors in multiple sclerosis. Brain 126:1755-1766.
43. Gispen WH, Adan RA. 1999. Melanocortins and the treatment of nervous system disease. Potential relevance to the skin? Ann N Y Acad Sci 885:342-349.
44. Giuliani D, Zaffe D, Ottani A, Spaccapelo L, Galantucci M, Minutoli L, Bitto A, Irrera N, Contri M, Altavilla D, Botticelli AR, Squadrito F, Guarini S. 2011. Treatment of cerebral ischemia with melanocortins acting at MC(4) receptors induces marked neurogenesis and long-lasting functional recovery. Acta Neuropathol 122:443-453.
45. Glaser GH, Merritt HH. 1951. Effects of ACTH and cortisone in multiple sclerosis. Trans Am Neuro Assoc 56:130-133.
46. Grinspan JB, Stern JL, Pustilnik SM, Pleasure D. 1990. Cerebral white matter contains PDGF responsive precursors to O2A cells. J Neurosci 10:1866-1873.
47. Guo F, Maeda Y, Ko EM, Delgado M, Horiuchi M, Soulika A, Miers L, Burns T, Itoh T, Shen H, Lee E, Sohn J, Pleasure D. 2012. Disruption of NMDA receptors in oligodendroglial lineage cells does not alter their susceptibility to experimental autoimmune encephalomyelitis or their normal development. J Neurosci 32:639-645.
48. Herbert JM, Seban E, Maffrand JP. 1990. Characterization of specific binding sites for [3H]-staurosporine on various protein kinases. Biochem Biophys Res Commun 171:189-195.
49. Jack C, Antel J, Brück W, Kuhlmann T. 2007. Contrasting potential of nitric oxide and peroxynitrite to mediate oligodendrocyte injury in multiple sclerosis. Glia 55:926-934.
50. Krohn AJ, Preis E, Prehn JH. 1998. Staurosporine-induced apoptosis of cultured rat hippocampal neurons involves caspase-1-like proteases as upstream initiators and increased production of superoxide as a main downstream effector. J Neurosci 18:8186-8197.
51. Lisak RP, Bealmear B, Nedelkoska L, Benjamins JA. 2006b. Secretory products of central nervous system glial cells induce Schwann cell proliferation and protect from cytokine-mediated death. J Neurosci Res 83:1425-1431.
52. Lisak RP, Benjamins JA, Bealmear B, Nedelkoska L, Yao B, Land S, Studzinski D. 2007. Differential effects of Th1, monocyte/macrophage and Th2 cytokine mixtures on early gene expression for glial and neural-related molecules in central nervous system mixed glial cell cultures: Neurotrophins, growth factors and structural proteins. J Neuroinflammation 4:30.
53. Lisak RP, Benjamins JA, Bealmear B, Nedelkoska L, Studzinski D, Retland E, Yao B, Land S. 2009. Differential effects of Th1, monocyte/macrophage and Th2 cytokine mixtures on early gene expression for molecules associated with metabolism, signaling and regulation in central nervous system mixed glial cell cultures. J Neuroinflammation 6:4.
54. Lisak RP, Benjamins JA, Bealmear B, Yao B, Land S, Nedelkoska L, Skundric D. 2006a. Differential effects of Th1, monocyte/macrophage and Th2 cytokine mixtures on early gene expression for immune-related molecules by central nervous system mixed glial cell cultures. Mult Scler 12:149-168.
55. Manning SM, Talos DM, Zhou C, Selip DB, Park HK, Park CJ, Volpe JJ, Jensen FE. 2008. NMDA receptor blockade with memantine attenuates white matter injury in a rat model of periventricular leukomalacia. J Neurosci 28:6670-6678.
56. Martinelli V, Rocca MA, Annovazzi P, Pulizzi A, Rodegher M, Martinelli Boneschi F, Scotti R, Falini A, Sormani MP, Comi G, Filippi M. 2009. A short-term randomized MRI study of high-dose oral vs intravenous methylprednisolone in MS. Neurology 73:1842-1848.
57. Matute C. 2011. Glutamate and ATP signalling in white matter pathology. J Anat 219:53-64.
58. Matute C, Alberdi E, Domercq M, Sánchez-Gómez MV, Pérez-Samartín A, Rodríguez-Antigüedad A, Pérez-Cerdá F. 2007. Excitotoxic damage to white matter. J Anat 210:693-702.
59. Milanese C, La Mantia L, Salmaggi A, Campi A, Eoli M, Scaioli V, Nespolo A, Corridori F. 1989. Double-blind randomized trial of ACTH versus dexamethasone versus methylprednisolone in multiple sclerosis bouts. Clinical, cerebrospinal fluid and neurophysiological results. Eur Neurol 29:10-14.
60. Moroni F, Cozzi A, Sili M, Mannaioni G. 2012. Kynurenic acid: A metabolite with multiple actions and multiple targets in brain and periphery. J Neural Transm 119:133-139.
61. Morrow SA, Stoian CA, Dmitrovic J, Chan SC, Metz LM. 2004. The bioavailability of IV methylprednisolone and oral prednisone in multiple sclerosis. Neurology 63:1079-1080.
62. Mountjoy KG. 2010. Distribution and function of melanocortin receptors within the brain. Adv Exp Med Biol 681:29-48.
63. Moyer AW, Jervis GA, Black J, Koprowski H, Cox HR. 1950. Action of adrenocorticotropic hormone (ACTH) in experimental allergic encephalomyelitis of the guinea pig. 75:387-390.
64. Mytinger JR, Joshi S. 2012. The current evaluation and treatment of infantile spasms among members of the child neurology society. J Child Neurol 27:1289-1294.
65. Nedelkoska L, Benjamins JA. 1998. Binding of cholera toxin B subunit: A surface marker for murine microglia but not oligodendrocytes or astrocytes. J Neurosci Res 53:605-612.
66. Newcombe J, Uddin A, Dove R, Patel B, Turski L, Nishizawa Y, Smith T. 2008. Glutamate receptor expression in multiple sclerosis lesions. Brain Pathol 18:52-61.
67. Noseworthy JH, Lucchinetti C, Rodriguez M, Weinshenker BG. 2000. Multiple sclerosis. N Engl J Med 343:938-952.
68. Oka A, Belliveau MJ, Rosenberg PA, Volpe JJ. 1993. Vulnerability of oligodendroglia to glutamate: pharmacology, mechanisms, and prevention. J Neurosci 13:1441-1453.
69. Perumal JS, Caon C, Hreha S, Zabad R, Tselis A, Lisak R, Khan O. 2008. Oral prednisone taper Following intravenous steroids fails to improve disability or recovery from relapses in multiple sclerosis. Eur J Neurol 15:677-680.
70. Pitt D, Nagelmeier IE, Wilson HC, Raine CS. 2003. Glutamate uptake by oligodendrocytes: Implications for excitotoxicity in multiple sclerosis. Neurology 61:1113-1120.
71. Pitt D, Werner P, Raine CS. 2000. Glutamate excitotoxicity in a model of multiple sclerosis. Nat Med 6:67-70.
72. Pitzalis C, Sharrack B, Gray IA, Lee A, Hughes RA. 1997. Comparison of the effects of oral versus intravenous methylprednisolone regimens on peripheral blood T lymphocyte adhesion molecule expression, T cell subsets distribution and TNF alpha concentrations in multiple sclerosis. J Neuroimmunol 74:62-68.
73. Raff MC, Mirsky R, Fields KL, Lisak RP, Dorfman SH, Silberberg DH, Gregson NA, Leibowitz S, Kennedy MC. 1978. Galactocerebroside is a specific cell-surface antigenic marker for oligodendrocytes in culture. Nature 274:813-816.
74. Ranscht B, Clapshaw PA, Price J, Noble M, Seifert W. 1982. Development of oligodendrocytes and Schwann cells studied with a monoclonal antibody against galactocerebroside. Proc Natl Acad Sci U S A 79:2709-2713.
75. Rose AS, Kuzma JW, Kurtzke JF, Namerow NS, Sibley WA, Tourtellotte WW. 1970. Cooperative study in the evaluation of therapy in multiple sclerosis. ACTH vs. placebo-Final report. Neurology 20:1-59.
76. Rosenberg PA, Dai W, Gan XD, Ali S, Fu J, Back SA, Sanchez RM, Segal MM, Follett PL, Jensen FE, Volpe JJ. 2003. Mature myelin basic protein-expressing oligodendrocytes are insensitive to kainate toxicity. J Neurosci Res 71:237-245.
77. Rosin C, Bates TE, Skaper SD. 2004. Excitatory amino acid induced oligodendrocyte cell death in vitro: Receptor-dependent and -independent mechanisms. J Neurochem 90:1173-1185.
78. Rüegg UT, Burgess GM. 1989. Staurosporine, K- 252 and UCN-01: Potent but nonspecific inhibitors of protein kinases. Trends Pharmacol Sci 10:218-220.
79. Sadasivan S, Zhang Z, Larner SF, Liu MC, Zheng W, Kobeissy FH, Hayes RL, Wang KK. 2010. Acute NMDA toxicity in cultured rat cerebellar granule neurons is accompanied by autophagy induction and late onset autophagic cell death phenotype. BMC Neurosci 11:21.
80. Salomon Y, Zohar M, Dejordy JO, Eshel Y, Shafir I, Leiba H, Garty N, Schmidt-Sole J, Azrad A, Shai E, Degani H. 1993. Signaling mechanisms controlled by melanocortins in melanoma, lacrimal, and brain astroglial cells. Ann N Y Acad Sci 680:364-380.
81. Sas K, Robotka H, Toldi J, Vécsei L. 2007. Mitochondria, metabolic disturbances, oxidative stress and the kynurenine system, with focus on neurodegenerative disorders. J Neurol Sci 257:221-239.
82. Selkirk JV, Nottebaum LM, Lee J, Yang W, Foster AC, Lechner SM. 2007. Identification of differential melanocortin 4 receptor agonist profiles at natively expressed receptors in rat cortical astrocytes and recombinantly expressed receptors in human embryonic kidney cells. Neuropharmacology 52:459-466.
83. Srinivasan R, Sailasuta N, Hurd R, Nelson S, Pelletier D. 2005. Evidence of elevated glutamate in multiple sclerosis using magnetic resonance spectroscopy at 3 T. Brain 128:1016-1025.
84. Stafstrom CE, Arnason BG, Baram TZ, Catania A, Cortez MA, Glauser TA, Pranzatelli MR, Riikonen R, Rogawski MA, Shinnar S, Swann JW. 2011. Treatment of infantile spasms: emerging insights from clinical and basic science perspectives. J Child Neurol 26:1411-1421.
85. Stone TW, Forrest CM, Darlington GL. 2012. Kynurenine pathway inhibition as a therapeutic strategy for neuroprotection. FEBS J 279:1386-1397.
86. Sun YY, Wang CY, Hsu MF, Juan SH, Chang CY, Chou CM, Yang LY, Hung KS, Xu J, Lee YH, Hsu CY. 2010. Glucocorticoid protection of oligodendrocytes against excitotoxin involving hypoxia-inducible factor-1alpha in a cell-type-specific manner. J Neurosci 30:9621-9630.
87. ++ dependent protein kinase. Biochem Biophys Res Commun 135:397-402.
88. Taylor AW, Kitaichi N. 2008. The diminishment of experimental autoimmune encephalomyelitis (EAE) by neuropeptide alpha-melanocyte stimulating hormone (alpha-MSH) therapy. Brain Behav Immun 22:639-646.
89. Teare KA, Pearson RG, Shakesheff KM, Haycock JW. 2004. Alpha-MSH inhibits inflammatory signalling in Schwann cell. Neuroreport 15:493-498.
90. Thompson AJ, Kennard C, Swash M, Summers B, Yuill GM, Shepherd DI, Roche S, Perkin GD, Loizou LA, Ferner R, Hughes R, Thompson M, Hand J. 1989. Relative efficacy of intravenous methylprednisolone and ACTH in the treatment of acute relapse in MS. Neurology 39:969-971.
91. Vamos E, Pardutz A, Klivenyi P, Toldi J, Vecsei L. 2009. The role of kynurenines in disorders of the central nervous system: Possibilities for neuroprotection. J Neurol Sci 283:21-27.
92. Volpe JJ, Kinney HC, Jensen FE, Rosenberg PA. 2011. The developing oligodendrocyte: Key cellular target in brain injury in the premature infant. Int J Dev Neurosci 29:423-440.
93. Werner P, Pitt D, Raine CS. 2001. Multiple sclerosis: Altered glutamate homeostasis in lesions correlates with oligodendrocyte and axonal damage. Ann Neurol 50:169-180.
94. Xia Y, Wikberg JE. 1997. Postnatal expression of melanocortin-3 receptor in rat diencephalon and mesencephalon. Neuropharmacology 36:217-224.
95. Xia Y, Wikberg JE, Chhajlani V. 1995. Expression of melanocortin 1 receptor in periaqueductal gray matter. Neuroreport 6:2193-2196.
96. Yoshioka A, Hardy M, Younkin DP, Grinspan JB, Stern JL, Pleasure D. 1995. Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors mediate excitotoxicity in the oligodendroglial lineage. J Neurochem 64:2442-2448.
97. Yoshioka A, Shimizu Y, Hirose G, Kitasato H, Pleasure D. 1998. Cyclic AMP-elevating agents prevent oligodendroglial excitotoxicity. J Neurochem 70:2416-2423.
98. Yoshioka A, Yamaya Y, Saiki S, Kanemoto M, Hirose G, Beesley J, Pleasure D. 2000. Non- N-methyl-d-aspartate glutamate receptors mediate oxygen-Glucose deprivation-induced oligodendroglial injury. Brain Res 854:207-215.
99. Zohar M, Salomon Y. 1992. Melanocortins stimulate proliferation and induce morphological changes in cultured rat astrocytes by distinct transducing mechanisms. Brain Res 576:49-58.