Curcumin Treatment Improves Motor Behavior in α-Synuclein Transgenic Mice

• Published in: PloS one Vol. 10; no. 6; p. e0128510
• Main Authors: Spinelli, Kateri J, Osterberg, Valerie R, Meshul, Charles K, Soumyanath, Amala, Unni, Vivek K
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 02.06.2015; Public Library of Science (PLoS)
• Subjects: Agglomeration; alpha-Synuclein - physiology; Animal models; Animals; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Behavior, Animal - drug effects; Blotting, Western; Chromatography, Liquid; Cortex; Curcumin; Curcumin - pharmacology; Dementia - drug therapy; Dementia - pathology; Diet; Dietary supplements; Female; Gait; Humans; Immunoenzyme Techniques; Intervention; Kinases; Lewy Bodies - drug effects; Lewy Bodies - pathology; Male; Metabolism; Mice; Mice, Transgenic; Molecular chains; Motor Activity - drug effects; Neurodegenerative diseases; Neurological diseases; Phosphorylation - drug effects; Plasma levels; Proteinase; Rodents; Science; Synuclein; Tandem Mass Spectrometry; Terminals; Transgenic mice; Oregon; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0128510

The curry spice curcumin plays a protective role in mouse models of neurodegenerative diseases, and can also directly modulate aggregation of α-synuclein protein in vitro, yet no studies have described the interaction of curcumin and α-synuclein in genetic synucleinopathy mouse models. Here we examined the effect of chronic and acute curcumin treatment in the Syn-GFP mouse line, which overexpresses wild-type human α-synuclein protein. We discovered that curcumin diet intervention significantly improved gait impairments and resulted in an increase in phosphorylated forms of α-synuclein at cortical presynaptic terminals. Acute curcumin treatment also caused an increase in phosphorylated α-synuclein in terminals, but had no direct effect on α-synuclein aggregation, as measured by in vivo multiphoton imaging and Proteinase-K digestion. Using LC-MS/MS, we detected ~5 ng/mL and ~12 ng/mL free curcumin in the plasma of chronic or acutely treated mice, with a glucuronidation rate of 94% and 97%, respectively. Despite the low plasma levels and extensive metabolism of curcumin, these results show that dietary curcumin intervention correlates with significant behavioral and molecular changes in a genetic synucleinopathy mouse model that mimics human disease.