 |
 Previous Article | Next Article 
The Journal of Neuroscience, December 1, 2000, 20(23):8597-8603
Growth/Differentiation Factor-15/Macrophage Inhibitory
Cytokine-1 Is a Novel Trophic Factor for Midbrain Dopaminergic
Neurons In Vivo
Jens
Strelau1,
Aideen
Sullivan2,
Martina
Böttner1,
Paul
Lingor1,
Elisabeth
Falkenstein3,
Clemens
Suter-Crazzolara1,
Dagmar
Galter1,
Jozsef
Jaszai1,
Kerstin
Krieglstein4, and
Klaus
Unsicker1
1 Neuroanatomy and Interdisciplinary Center for
Neurosciences, University of Heidelberg, D-69120 Heidelberg, Germany,
2 Department of Anatomy, University College, Cork,
Ireland, 3 Department of Clinical Pharmacology,
Faculty for Clinical Medicine, University of Heidelberg, D-68167
Mannheim, Germany, and 4 Department of Anatomy, University
of the Saarland, D-66421 Homburg, Germany
Transforming growth factor- s (TGF-s) constitute an expanding
family of multifunctional cytokines with prominent roles in development, cell proliferation, differentiation, and repair. We have
cloned, expressed, and raised antibodies against a distant member of
the TGF-s, growth/differentiation factor-15 (GDF-15). GDF-15 is
identical to macrophage inhibitory cytokine-1 (MIC-1). GDF-15/MIC-1
mRNA and protein are widely distributed in the developing and adult CNS
and peripheral nervous systems, including choroid plexus and CSF.
GDF-15/MIC-1 is a potent survival promoting and protective factor for
cultured and iron-intoxicated dopaminergic (DAergic) neurons cultured
from the embryonic rat midbrain floor. The trophic effect of
GDF-15/MIC-1 was not accompanied by an increase in cell proliferation
and astroglial maturation, suggesting that GDF-15/MIC-1 probably acts
directly on neurons. GDF-15/MIC-1 also protects 6-hydroxydopamine
(6-OHDA)-lesioned nigrostriatal DAergic neurons in vivo.
Unilateral injections of GDF-15/MIC-1 into the medial forebrain bundle
just above the substantia nigra (SN) and into the left ventricle (20 µg each) immediately before a 6-OHDA injection (8 µg) prevented
6-OHDA-induced rotational behavior and significantly reduced losses of
DAergic neurons in the SN. This protection was evident for at least 1 month. Administration of 5 µg of GDF-15/MIC-1 in the same paradigm
also provided significant neuroprotection. GDF-15/MIC-1 also promoted
the serotonergic phenotype of cultured raphe neurons but did not
support survival of rat motoneurons. Thus, GDF-15/MIC-1 is a novel
neurotrophic factor with prominent effects on DAergic and serotonergic
neurons. GDF-15/MIC-1 may therefore have a potential for the treatment
of Parkinson's disease and disorders of the serotonergic system.
Key words:
GDF-15/MIC-1; TGF-; dopaminergic neurons; 6-OHDA; Parkinson's disease; neurotrophic factor
Copyright © 2000 Society for Neuroscience 0270-6474/00/20238597-07$05.00/0
This article has been cited by other articles:
|
|
|
|
 
J. Strelau, A. Strzelczyk, P. Rusu, G. Bendner, S. Wiese, F. Diella, A. L. Altick, C. S. von Bartheld, R. Klein, M. Sendtner, et al.
Progressive Postnatal Motoneuron Loss in Mice Lacking GDF-15
J. Neurosci.,
October 28, 2009;
29(43):
13640 - 13648.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Yoshioka, H. Kamitani, T. Watanabe, and T. E. Eling
Nonsteroidal Anti-inflammatory Drug-activated Gene (NAG-1/GDF15) Expression Is Increased by the Histone Deacetylase Inhibitor Trichostatin A
J. Biol. Chem.,
November 28, 2008;
283(48):
33129 - 33137.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Koike, Y. Kassai, Y. Kouta, H. Miwa, M. Konishi, and N. Itoh
Brorin, a Novel Secreted Bone Morphogenetic Protein Antagonist, Promotes Neurogenesis in Mouse Neural Precursor Cells
J. Biol. Chem.,
May 25, 2007;
282(21):
15843 - 15850.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Kempf, R. Horn-Wichmann, G. Brabant, T. Peter, T. Allhoff, G. Klein, H. Drexler, N. Johnston, L. Wallentin, and K. C. Wollert
Circulating Concentrations of Growth-Differentiation Factor 15 in Apparently Healthy Elderly Individuals and Patients with Chronic Heart Failure as Assessed by a New Immunoradiometric Sandwich Assay
Clin. Chem.,
February 1, 2007;
53(2):
284 - 291.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Boyer, W. L. Allen, E. G. McLean, P. M. Wilson, A. McCulla, S. Moore, D. B. Longley, C. Caldas, and P. G. Johnston
Pharmacogenomic identification of novel determinants of response to chemotherapy in colon cancer.
Cancer Res.,
March 1, 2006;
66(5):
2765 - 2777.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. A. Brown, C. Stephan, R. L. Ward, M. Law, M. Hunter, A. R. Bauskin, J. Amin, K. Jung, E. P. Diamandis, G. M. Hampton, et al.
Measurement of Serum Levels of Macrophage Inhibitory Cytokine 1 Combined with Prostate-Specific Antigen Improves Prostate Cancer Diagnosis
Clin. Cancer Res.,
January 1, 2006;
12(1):
89 - 96.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. D. Kraft, D. A. Johnson, and J. A. Johnson
Nuclear Factor E2-Related Factor 2-Dependent Antioxidant Response Element Activation by tert-Butylhydroquinone and Sulforaphane Occurring Preferentially in Astrocytes Conditions Neurons against Oxidative Insult
J. Neurosci.,
February 4, 2004;
24(5):
1101 - 1112.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Yang, Z. Filipovic, D. Brown, S. N. Breit, and L. T. Vassilev
Macrophage inhibitory cytokine-1: A novel biomarker for p53 pathway activation
Mol. Cancer Ther.,
October 1, 2003;
2(10):
1023 - 1029.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
T. Liu, A. R. Bauskin, J. Zaunders, D. A. Brown, S. Pankurst, P. J. Russell, and S. N. Breit
Macrophage Inhibitory Cytokine 1 Reduces Cell Adhesion and Induces Apoptosis in Prostate Cancer Cells
Cancer Res.,
August 15, 2003;
63(16):
5034 - 5040.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Holzschuh, G. Hauptmann, and W. Driever
Genetic Analysis of the Roles of Hh, FGF8, and Nodal Signaling during Catecholaminergic System Development in the Zebrafish Brain
J. Neurosci.,
July 2, 2003;
23(13):
5507 - 5519.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. A. Brown, R. L. Ward, P. Buckhaults, T. Liu, K. E. Romans, N. J. Hawkins, A. R. Bauskin, K. W. Kinzler, B. Vogelstein, and S. N. Breit
MIC-1 Serum Level and Genotype: Associations with Progress and Prognosis of Colorectal Carcinoma
Clin. Cancer Res.,
July 1, 2003;
9(7):
2642 - 2650.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Subramaniam, J. Strelau, and K. Unsicker
Growth Differentiation Factor-15 Prevents Low Potassium-induced Cell Death of Cerebellar Granule Neurons by Differential Regulation of Akt and ERK Pathways
J. Biol. Chem.,
March 7, 2003;
278(11):
8904 - 8912.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Monks, E. Harris, C. Hose, J. Connelly, and E. A. Sausville
Genotoxic Profiling of MCF-7 Breast Cancer Cell Line Elucidates Gene Expression Modifications Underlying Toxicity of the Anticancer Drug 2-(4-Amino-3-methylphenyl)-5-fluorobenzothiazole
Mol. Pharmacol.,
March 1, 2003;
63(3):
766 - 772.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. D. Pavelko, C. L. Howe, K. M. Drescher, J. D. Gamez, A. J. Johnson, T. Wei, R. M. Ransohoff, and M. Rodriguez
Interleukin-6 Protects Anterior Horn Neurons from Lethal Virus-Induced Injury
J. Neurosci.,
January 15, 2003;
23(2):
481 - 492.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. K. Wirtz, J. R. Samples, H. Xu, T. Severson, and T. S. Acott
Expression Profile and Genome Location of cDNA Clones from an Infant Human Trabecular Meshwork Cell Library
Invest. Ophthalmol. Vis. Sci.,
December 1, 2002;
43(12):
3698 - 3704.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. B. Welsh, L. M. Sapinoso, A. I. Su, S. G. Kern, J. Wang-Rodriguez, C. A. Moskaluk, H. F. Frierson Jr., and G. M. Hampton
Analysis of Gene Expression Identifies Candidate Markers and Pharmacological Targets in Prostate Cancer
Cancer Res.,
August 1, 2001;
61(16):
5974 - 5978.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. D. Fairlie, H.-P. Zhang, W. M. Wu, S. L. Pankhurst, A. R. Bauskin, P. K. Russell, P. K. Brown, and S. N. Breit
The Propeptide of the Transforming Growth Factor-beta Superfamily Member, Macrophage Inhibitory Cytokine-1 (MIC-1), Is a Multifunctional Domain That Can Facilitate Protein Folding and Secretion
J. Biol. Chem.,
May 11, 2001;
276(20):
16911 - 16918.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
