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Oral administration of Pantoea agglomerans-derived lipopolysaccharide prevents metabolic dysfunction and Alzheimer’s disease-related memory loss in senescence-accelerated prone 8 (SAMP8) mice fed a high-fat diet

by Yutaro Kobayashi, Hiroyuki Inagawa, Chie Kohchi, Kimiko Kazumura, Hiroshi Tsuchiya, Toshiyuki Miwa, Katsuichiro Okazaki, Gen-Ichiro Soma

The pathogenesis of Alzheimer’s disease (AD) remains unclear, but an imbalance between the production and clearance of amyloid-β (Aβ) peptides is known to play a critical role in AD progression. A promising preventative approach is to enhance the normal Aβ clearance activity of brain phagocytes such as microglia. In mice, the intraperitoneal injection of Toll-like receptor 4 agonist was shown to enhance Aβ clearance and exhibit a preventative effect on AD-related pathology. Our previous clinical study demonstrated that orally administered Pantoea agglomerans-derived lipopolysaccharide (LPSp) exhibited an LDL (low-density lipoprotein)-lowering effect in human volunteers with hyperlipidemia, a known risk factor for AD. In vitro studies have shown that LPSp treatment increases Aβ phagocytosis by microglial cells; however it is still unclear whether orally administered LPSp exhibits a preventive effect on AD progression. We show here that in senescence-accelerated prone 8 (SAMP8) mice fed a high-fat diet, oral administration of LPSp at 0.3 or 1 mg/kg body weight·day for 18 weeks significantly improved glucose metabolism and lipid profiles. The LPSp treatment also reduced pro-inflammatory cytokine expression and oxidative-burst activity in the peripheral blood. Moreover, LPSp significantly reduced brain Aβ burden and memory impairment as seen in the water maze test, although we could not confirm a significant enhancement of Aβ phagocytosis in microglia isolated from the brains after treatment. Taken together, our results show that LPSp holds promise as a preventative therapy for AD or AD-related diseases induced by impairment of metabolic functions.

Authors:   Yutaro Kobayashi; Hiroyuki Inagawa; Chie Kohchi; Kimiko Kazumura; Hiroshi Tsuchiya; Toshiyuki Miwa; Katsuichiro Okazaki; Gen-Ichiro Soma
Journal:   PLoS ONE
Volume:   13
edition:   6
Year:   2018
Pages:   e0198493
DOI:   10.1371/journal.pone.0198493
Publication date:   01-Jun-2018
Facts, background information, dossiers
  • phagocytosis
  • microglia
  • lipopolysaccharide
More about PLoS ONE
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