Neuroprotective effects of bee venom phospholipase A2 in the 3xTg AD mouse model of Alzheimer's disease

J Neuroinflammation. 2016 Jan 16;13:10. doi: 10.1186/s12974-016-0476-z.

Abstract

Background: Alzheimer's disease (AD) is a severe neuroinflammatory disease. CD4(+)Foxp3(+) regulatory T cells (Tregs) modulate various inflammatory diseases via suppressing Th cell activation. There are increasing evidences that Tregs have beneficial roles in neurodegenerative diseases. Previously, we found the population of Treg cells was significantly increased by bee venom phospholipase A2 (bvPLA2) treatment in vivo and in vitro.

Methods: To examine the effects of bvPLA2 on AD, bvPLA2 was administered to 3xTg-AD mice, mouse model of Alzheimer's disease. The levels of amyloid beta (Aβ) deposits in the hippocampus, glucose metabolism in the brain, microglia activation, and CD4(+) T cell infiltration were analyzed to evaluate the neuroprotective effect of bvPLA2.

Results: bvPLA2 treatment significantly enhanced the cognitive function of the 3xTg-AD mice and increased glucose metabolism, as assessed with 18F-2 fluoro-2-deoxy-D-glucose ([F-18] FDG) positron emission tomography (PET). The levels of Aβ deposits in the hippocampus were dramatically decreased by bvPLA2 treatment. This neuroprotective effect of bvPLA2 was associated with microglial deactivation and reduction in CD4(+) T cell infiltration. Interestingly, the neuroprotective effects of bvPLA2 were abolished in Treg-depleted mice.

Conclusions: The present studies strongly suggest that the increase of Treg population by bvPLA2 treatment might inhibit progression of AD in the 3xTg AD mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / complications
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / genetics
  • Alzheimer Disease / pathology
  • Amyloid beta-Protein Precursor / genetics
  • Animals
  • Antigens, CD / metabolism
  • Bee Venoms / chemistry
  • Body Weight / drug effects
  • Body Weight / genetics
  • Disease Models, Animal
  • Escape Reaction / drug effects
  • Fluorodeoxyglucose F18 / pharmacokinetics
  • Hippocampus / diagnostic imaging
  • Hippocampus / pathology
  • Humans
  • Learning Disabilities / drug therapy
  • Learning Disabilities / etiology
  • Maze Learning / drug effects
  • Maze Learning / physiology
  • Mice
  • Mice, Transgenic
  • Mutation / genetics
  • Neuroprotective Agents / therapeutic use*
  • Phospholipases A2 / therapeutic use*
  • Presenilin-1 / genetics
  • Radionuclide Imaging
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / physiology
  • tau Proteins / genetics

Substances

  • Amyloid beta-Protein Precursor
  • Antigens, CD
  • Bee Venoms
  • Neuroprotective Agents
  • PSEN1 protein, human
  • Presenilin-1
  • tau Proteins
  • Fluorodeoxyglucose F18
  • Phospholipases A2