title: Ibuprofen ameliorates protein aggregation and astrocytic gliosis, but not cognitive dysfunction, in a transgenic mouse expressing dementia with Lewy bodies-linked P123H β-synuclein.
abstract: Epidemiological studies have shown that ibuprofen, a non-steroidal anti-inflammatory drug, reduces the risk for neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). In this context, it has been shown that chronic treatment with ibuprofen improves cognitive dysfunction and histopathologic outcome in mouse models of AD. However, the therapeutic effects of ibuprofen in animal models of PD and related synucleinopathies such as dementia with Lewy bodies (DLB) have not been investigated. Therefore, the main objective of this study was to determine if ibuprofen ameliorates neuropathology and cognitive dysfunction in a transgenic (tg) mouse expressing DLB-linked P123H β-synuclein. P123H β-synuclein tg mice and their non-tg littermates aged 3 months were given ibuprofen in their diet (n=13). Controls did not receive ibuprofen (n=11). After 3 months, the mice were evaluated using a Morris water maze test, followed by neuropathological analyses. Compared to control P123H β-synuclein tg mice, P123H β-synuclein tg mice that received ibuprofen had significantly reduced protein aggregation and astrogliosis. However, ibuprofen treatment produced little improvement of the learning disability of P123H β-synuclein tg mice in the Morris water maze test. These results suggest that amelioration of neuropathologies by ibuprofen does not necessarily lead to improved cognitive function in synucleinopathies such as DLB.
authors.affiliation: Division of Sensory and Motor Systems, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-0057, Japan.
authors.forename: Kazunari
authors.initials: K
authors.lastname: Sekiyama
authors.forename: Masayo
authors.initials: M
authors.lastname: Fujita
authors.forename: Akio
authors.initials: A
authors.lastname: Sekigawa
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Takamatsu
authors.forename: Masaaki
authors.initials: M
authors.lastname: Waragai
authors.forename: Takato
authors.initials: T
authors.lastname: Takenouchi
authors.forename: Shuei
authors.initials: S
authors.lastname: Sugama
authors.forename: Makoto
authors.initials: M
authors.lastname: Hashimoto
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D003072:Cognition Disorders / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D005911:Gliosis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D007052:Ibuprofen / Q000494:pharmacology / Q000627:therapeutic use*; D016631:Lewy Bodies / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D020961:Lewy Body Disease / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D051846:beta-Synuclein / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D051846:beta-Synuclein; D007052:Ibuprofen