Curcumin therapy in a Plp1 transgenic mouse model of Pelizaeus‐Merzbacher disease. Issue 8 (24th June 2015)

• Record Type: Journal Article
• Authors: Epplen, Dirk B.; Prukop, Thomas; Nientiedt, Tobias; Albrecht, Philipp; Arlt, Friederike A.; Stassart, Ruth M.; Kassmann, Celia M.; Methner, Axel; Nave, Klaus‐Armin; Werner, Hauke B.; Sereda, Michael W.
• Is Part Of: Annals of clinical and translational neurology. Volume 2:Issue 8(2015:Aug.)
• Page Start: 787
• Page End: 796
• Publication Date: 2015-06-24
• Subjects: Nervous system -- Diseases -- Periodicals; Neurology -- Periodicals; 616.8005
• DOI: 10.1002/acn3.219
• Languages: English
• ISSNs: 2328-9503

Abstract

<abstract abstract-type="main" id="acn3219-abs-0001"> <title>Abstract</title> <sec id="acn3219-sec-0001" sec-type="section"> <title>Objective</title> <p>Pelizaeus–Merzbacher disease (PMD) is a progressive and lethal leukodystrophy caused by mutations affecting the proteolipid protein (<italic>PLP1</italic>) gene. The most common cause of PMD is a duplication of <italic>PLP1</italic> and at present there is no curative therapy available.</p> </sec> <sec id="acn3219-sec-0002" sec-type="section"> <title>Methods</title> <p>By using transgenic mice carrying additional copies of <italic>Plp1</italic>, we investigated whether curcumin diet ameliorates PMD symptoms. The diet of <italic>Plp1</italic> transgenic mice was supplemented with curcumin for 10 consecutive weeks followed by phenotypical, histological and immunohistochemical analyses of the central nervous system. <italic>Plp1</italic> transgenic and wild‐type mice fed with normal chow served as controls.</p> </sec> <sec id="acn3219-sec-0003" sec-type="section"> <title>Results</title> <p>Curcumin improved the motor phenotype performance of <italic>Plp1</italic> transgenic mice by 50% toward wild‐type level and preserved myelinated axons by 35% when compared to <italic>Plp1</italic> transgenic controls. Furthermore, curcumin reduced astrocytosis, microgliosis and lymphocyte infiltration in <italic>Plp1</italic> transgenic mice. Curcumin diet did not affect the pathologically increased <italic>Plp1 </italic>mRNA abundance. However, high glutathione levels indicating an oxidative misbalance in the white matter of <italic>Plp1</italic> transgenic mice were restored by curcumin treatment.</p> </sec> <sec id="acn3219-sec-0004" sec-type="section"> <title>Interpretation</title> <p>Curcumin may potentially serve as an antioxidant therapy of PMD caused by <italic>PLP1</italic> gene duplication.</p> </sec> </abstract>