title: Curcumin Treatment Improves Motor Behavior in α-Synuclein Transgenic Mice.
abstract: 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.
authors.affiliation: Jungers Center for Neurosciences Research, Oregon Health & Science University, Portland, Oregon, United States of America; Department of Neurology, Oregon Health & Science University, Portland, Oregon, United States of America.
authors.forename: Kateri J
authors.initials: KJ
authors.lastname: Spinelli
authors.affiliation: Jungers Center for Neurosciences Research, Oregon Health & Science University, Portland, Oregon, United States of America; Department of Neurology, Oregon Health & Science University, Portland, Oregon, United States of America.
authors.forename: Valerie R
authors.initials: VR
authors.lastname: Osterberg
authors.affiliation: Research Services, Veterans Affairs Medical Center, Portland, Oregon, United States of America; Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, Oregon, United States of America.
authors.forename: Charles K
authors.initials: CK
authors.lastname: Meshul
authors.affiliation: Department of Neurology, Oregon Health & Science University, Portland, Oregon, United States of America.
authors.forename: Amala
authors.initials: A
authors.lastname: Soumyanath
authors.affiliation: Jungers Center for Neurosciences Research, Oregon Health & Science University, Portland, Oregon, United States of America; Department of Neurology, Oregon Health & Science University, Portland, Oregon, United States of America; Parkinson Center of Oregon, Oregon Health & Science University, Portland, Oregon, United States of America.
authors.forename: Vivek K
authors.initials: VK
authors.lastname: Unni
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D015153:Blotting, Western; D002853:Chromatography, Liquid; D003474:Curcumin / Q000494:pharmacology*; D003704:Dementia / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D016631:Lewy Bodies / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D053719:Tandem Mass Spectrometry; D051844:alpha-Synuclein / Q000502:physiology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; C497604:SNCA protein, human; D051844:alpha-Synuclein; D003474:Curcumin