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Bee Venom Soluble Phospholipase A2 Exerts Neuroprotective Effects in a Lipopolysaccharide-Induced Mouse Model of Alzheimer’s Disease via Inhibition of Nuclear Factor-Kappa B

Authors
  • Ham, Hyeon Joo1
  • Han, Ji Hye1
  • Lee, Yong Sun1
  • Kim, Ki Cheon1
  • Yun, Jaesuk1
  • Kang, Shin Kook1
  • Park, YangSu1
  • Kim, Se Hyun2
  • Hong, Jin Tae1
  • 1 College of Pharmacy and Medical Research Center, Chungbuk National University, Chungbuk
  • 2 INISTst Company Limited, Gyeonggi-do
Type
Published Article
Journal
Frontiers in Aging Neuroscience
Publisher
Frontiers Media SA
Publication Date
Nov 01, 2019
Volume
11
Identifiers
DOI: 10.3389/fnagi.2019.00287
Source
Frontiers
Keywords
Disciplines
  • Neuroscience
  • Original Research
License
Green

Abstract

Neuroinflammation is important in the pathogenesis and development of Alzheimer’s disease (AD). In the AD brain, microglial activation and upregulation of pro-inflammatory mediators both induce amyloid beta (Aβ) accumulation. Regulatory T cells (Tregs) and nuclear factor-kappa B (NF-κB) signaling have been implicated in AD development through their effects on neuroinflammation and microglial activation. The bee venom soluble phospholipase A2 (bv-sPLA2) enzyme is known to exert anti-inflammatory and anti-immune effects. Here, we investigated the inhibitory effects of bv-sPLA2 on memory deficiency in a lipopolysaccharide (LPS)-induced mouse model of AD. We examined whether bv-sPLA2 (0.02, 0.2, and 2 mg/kg by i.p. injection three times for 1 week) could inhibit neuroinflammation and memory impairment in LPS-treated mice (250 μg/kg by i.p. injection daily for 1 week). We also assessed the effects of bv-sPLA2 administration (0.01, 0.1, and 1 μg/ml) on LPS (1 μg/ml)-treated microglial BV-2 cells. In the LPS-injected mouse brain, sPLA2 treatment rescued memory dysfunction and decreased Aβ levels, through the downregulation of amyloidogenic proteins, and decreased the expression of inflammatory proteins and pro-inflammatory cytokines. Moreover, the LPS-mediated increase in inflammatory protein expression was attenuated bv-sPLA2 treatment in BV-2 cells. Treatment with bv-sPLA2 also downregulated signaling by NF-κB, which is considered to be an important factor in the regulation of neuroinflammatory and amyloidogenic responses, both in vivo and in vitro. Additionally, co-treatment with NF-κB (5 μM) and bv-sPLA2 (0.1 μg/ml) exerted more marked anti-inflammatory effects, compared to bv-sPLA2 treatment alone. These results indicate that bv-sPLA2 inhibits LPS-induced neuroinflammation and amyloidogenesis via inhibition of NF-κB.

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