Curcumin therapy in a Plp1 transgenic mouse model of Pelizaeus-Merzbacher disease.
OBJECTIVE
Pelizaeus-Merzbacher disease (PMD) is a progressive and lethal leukodystrophy caused by mutations affecting the proteolipid protein (PLP1) gene. The most common cause of PMD is a duplication of PLP1 and at present there is no curative therapy available.


METHODS
By using transgenic mice carrying additional copies of Plp1, we investigated whether curcumin diet ameliorates PMD symptoms. The diet of Plp1 transgenic mice was supplemented with curcumin for 10 consecutive weeks followed by phenotypical, histological and immunohistochemical analyses of the central nervous system. Plp1 transgenic and wild-type mice fed with normal chow served as controls.


RESULTS
Curcumin improved the motor phenotype performance of Plp1 transgenic mice by 50% toward wild-type level and preserved myelinated axons by 35% when compared to Plp1 transgenic controls. Furthermore, curcumin reduced astrocytosis, microgliosis and lymphocyte infiltration in Plp1 transgenic mice. Curcumin diet did not affect the pathologically increased Plp1 mRNA abundance. However, high glutathione levels indicating an oxidative misbalance in the white matter of Plp1 transgenic mice were restored by curcumin treatment.


CONCLUSIONS
Curcumin may potentially serve as an antioxidant therapy of PMD caused by PLP1 gene duplication.
Department of Neurogenetics, Max-Planck-Institute of Experimental Medicine Göttingen, Germany.
Dirk B
DB
Epplen
Department of Neurogenetics, Max-Planck-Institute of Experimental Medicine Göttingen, Germany ; Institute of Clinical Pharmacology, University Medical Center Göttingen (UMG) Göttingen, Germany.
Thomas
T
Prukop
Department of Neurogenetics, Max-Planck-Institute of Experimental Medicine Göttingen, Germany.
Tobias
T
Nientiedt
Department of Neurology, Medical Faculty, Heinrich-Heine-University Düsseldorf, Germany.
Philipp
P
Albrecht
Department of Neurogenetics, Max-Planck-Institute of Experimental Medicine Göttingen, Germany.
Friederike A
FA
Arlt
Department of Neurogenetics, Max-Planck-Institute of Experimental Medicine Göttingen, Germany ; Institute of Neuropathology, University Medical Center Göttingen (UMG) Göttingen, Germany.
Ruth M
RM
Stassart
Department of Neurogenetics, Max-Planck-Institute of Experimental Medicine Göttingen, Germany.
Celia M
CM
Kassmann
Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn2), Department of Neurology, Johannes Gutenberg University Medical Center Mainz Mainz, Germany.
Axel
A
Methner
Department of Neurogenetics, Max-Planck-Institute of Experimental Medicine Göttingen, Germany.
Klaus-Armin
KA
Nave
Department of Neurogenetics, Max-Planck-Institute of Experimental Medicine Göttingen, Germany.
Hauke B
HB
Werner
Department of Neurogenetics, Max-Planck-Institute of Experimental Medicine Göttingen, Germany ; Department of Clinical Neurophysiology, University Medical Center Göttingen (UMG) Göttingen, Germany.
Michael W
MW
Sereda