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Curcumin therapy in a Plp1 transgenic mouse model of Pelizaeus-Merzbacher disease.

Epplen DB, Prukop T, Nientiedt T, Albrecht P, Arlt FA, Stassart RM, Kassmann CM, Methner A, Nave KA, Werner HB, Sereda MW - Ann Clin Transl Neurol (2015)

Bottom Line: Furthermore, curcumin reduced astrocytosis, microgliosis and lymphocyte infiltration in Plp1 transgenic mice.Curcumin diet did not affect the pathologically increased Plp1 mRNA abundance.Curcumin may potentially serve as an antioxidant therapy of PMD caused by PLP1 gene duplication.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurogenetics, Max-Planck-Institute of Experimental Medicine Göttingen, Germany.

ABSTRACT

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.

Interpretation: Curcumin may potentially serve as an antioxidant therapy of PMD caused by PLP1 gene duplication.

No MeSH data available.


Related in: MedlinePlus

Overview on the experimental treatment in Plp1 transgenic mice (A). Number of slips over a 2 m walking distance was increased at study start in both Plp1 transgenic groups compared to wild-type controls (B) and was decreased in Plp1 transgenic mice after chronic curcumin treatment (C). Also, curcumin dietary reduced present signs of body shaking in Plp1 transgenic mice (D). WT, wildt-ype; Plp1 tg, Plp1 transgenic homozygous line #72; mean ± SD; ns, not significant; *P < 0.05, **P < 0.01, ***P < 0.001.
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fig01: Overview on the experimental treatment in Plp1 transgenic mice (A). Number of slips over a 2 m walking distance was increased at study start in both Plp1 transgenic groups compared to wild-type controls (B) and was decreased in Plp1 transgenic mice after chronic curcumin treatment (C). Also, curcumin dietary reduced present signs of body shaking in Plp1 transgenic mice (D). WT, wildt-ype; Plp1 tg, Plp1 transgenic homozygous line #72; mean ± SD; ns, not significant; *P < 0.05, **P < 0.01, ***P < 0.001.

Mentions: The present study was performed in Plp1 transgenic mice applying a curcumin-containing diet ad libitum for 10 consecutive weeks. Plp1 transgenic and wild-type mice receiving normal chow served as controls (Fig.1A). At study start, 3-week-old Plp1 transgenic mice already showed an increased number of limb slips over a walking distance of 2 m compared to wild-type controls (9.0 ± 2.0 and 6.9 ± 2.4, P < 0.05) (Fig.1B). Ten weeks later, the difference between Plp1 transgenic mice and wild-type controls was further enhanced (15.3 ± 2.5 and 8.6 ± 3.0, P < 0.001). However, Plp1 transgenic mice treated with curcumin for 10 weeks had improved motor capabilities compared to Plp1 transgenic controls (11.3 ± 2.6, P < 0.01) although wild-type levels were not reached (P < 0.05; Fig.1C). Involuntary body shaking was generally not observed at the start of the study in all investigated groups including Plp1 transgenic and wild-type mice (data not shown) but was present at the end of the study in 42% of Plp1 transgenic controls. At this time point, wild-type mice still did not show any body shaking (0%, P < 0.001). Curcumin diet for 10 weeks successfully diminished the body shaking within the Plp1 transgenic group to 11% so that the body shaking was statistically indistinguishable from wild-type mice (Fig.1D).


Curcumin therapy in a Plp1 transgenic mouse model of Pelizaeus-Merzbacher disease.

Epplen DB, Prukop T, Nientiedt T, Albrecht P, Arlt FA, Stassart RM, Kassmann CM, Methner A, Nave KA, Werner HB, Sereda MW - Ann Clin Transl Neurol (2015)

Overview on the experimental treatment in Plp1 transgenic mice (A). Number of slips over a 2 m walking distance was increased at study start in both Plp1 transgenic groups compared to wild-type controls (B) and was decreased in Plp1 transgenic mice after chronic curcumin treatment (C). Also, curcumin dietary reduced present signs of body shaking in Plp1 transgenic mice (D). WT, wildt-ype; Plp1 tg, Plp1 transgenic homozygous line #72; mean ± SD; ns, not significant; *P < 0.05, **P < 0.01, ***P < 0.001.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4554440&req=5

fig01: Overview on the experimental treatment in Plp1 transgenic mice (A). Number of slips over a 2 m walking distance was increased at study start in both Plp1 transgenic groups compared to wild-type controls (B) and was decreased in Plp1 transgenic mice after chronic curcumin treatment (C). Also, curcumin dietary reduced present signs of body shaking in Plp1 transgenic mice (D). WT, wildt-ype; Plp1 tg, Plp1 transgenic homozygous line #72; mean ± SD; ns, not significant; *P < 0.05, **P < 0.01, ***P < 0.001.
Mentions: The present study was performed in Plp1 transgenic mice applying a curcumin-containing diet ad libitum for 10 consecutive weeks. Plp1 transgenic and wild-type mice receiving normal chow served as controls (Fig.1A). At study start, 3-week-old Plp1 transgenic mice already showed an increased number of limb slips over a walking distance of 2 m compared to wild-type controls (9.0 ± 2.0 and 6.9 ± 2.4, P < 0.05) (Fig.1B). Ten weeks later, the difference between Plp1 transgenic mice and wild-type controls was further enhanced (15.3 ± 2.5 and 8.6 ± 3.0, P < 0.001). However, Plp1 transgenic mice treated with curcumin for 10 weeks had improved motor capabilities compared to Plp1 transgenic controls (11.3 ± 2.6, P < 0.01) although wild-type levels were not reached (P < 0.05; Fig.1C). Involuntary body shaking was generally not observed at the start of the study in all investigated groups including Plp1 transgenic and wild-type mice (data not shown) but was present at the end of the study in 42% of Plp1 transgenic controls. At this time point, wild-type mice still did not show any body shaking (0%, P < 0.001). Curcumin diet for 10 weeks successfully diminished the body shaking within the Plp1 transgenic group to 11% so that the body shaking was statistically indistinguishable from wild-type mice (Fig.1D).

Bottom Line: Furthermore, curcumin reduced astrocytosis, microgliosis and lymphocyte infiltration in Plp1 transgenic mice.Curcumin diet did not affect the pathologically increased Plp1 mRNA abundance.Curcumin may potentially serve as an antioxidant therapy of PMD caused by PLP1 gene duplication.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurogenetics, Max-Planck-Institute of Experimental Medicine Göttingen, Germany.

ABSTRACT

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.

Interpretation: Curcumin may potentially serve as an antioxidant therapy of PMD caused by PLP1 gene duplication.

No MeSH data available.


Related in: MedlinePlus