Bee venom phospholipase A2 ameliorates Alzheimer’s disease pathology in Aβ vaccination treatment without inducing neuro-inflammation in a 3xTg-AD mouse model
| Autor: | Jin Su Kim, Young Jun Ye, Nam-sik Kim, Hyunjung Baek, Chanju Lee, Hyunsu Bae, Insop Shim, Da Bin Choi, Yong-Suk Kim, Youn-Sub Kim |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Pathology medicine.medical_specialty Transgene Glucose uptake CD3 Central nervous system lcsh:Medicine Inflammation Mice Transgenic tau Proteins T-Lymphocytes Regulatory Article 03 medical and health sciences Mice 0302 clinical medicine Phospholipase A2 Alzheimer Disease medicine Animals lcsh:Science Multidisciplinary Amyloid beta-Peptides biology business.industry Vaccination lcsh:R Meningoencephalitis Brain medicine.disease Peptide Fragments Mice Inbred C57BL Bee Venoms Disease Models Animal Phospholipases A2 030104 developmental biology medicine.anatomical_structure biology.protein lcsh:Q medicine.symptom business Cognition Disorders 030217 neurology & neurosurgery |
| Zdroj: | Scientific Reports, Vol 8, Iss 1, Pp 1-11 (2018) Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-018-35030-1 |
| Popis: | Alzheimer’s disease (AD) is the most common form of dementia and is characterized by an imbalance between the production and clearance of amyloid-beta (Aβ) and tau proteins. Although vaccination against Aβ peptide results in a dramatic reduction in Aβ pathology in experimental mouse models, the initial clinical trial for an active Aβ vaccine was halted early due to the development of acute meningoencephalitis in 6% of the immunized patients, which likely involved a T-cell mediated pro-inflammatory response. In this study, we aimed to determine whether bee venom phospholipase A2 (bvPLA2) treatment would induce Tregs and ameliorate AD pathology without unwanted T cell-mediated inflammation. First, we investigated the effects of bvPLA2 on the inflammatory infiltration caused by Aβ vaccination. Inflammatory aggregates of CD3+ T lymphocytes and macrophages were found in the brains and spinal cords of mice treated with Aβ. However, administration of bvPLA2 dramatically eliminated central nervous system inflammation following Aβ immunization. In AD model mice (3xTg-AD mice), bvPLA2 administration significantly ameliorated cognitive deficits and reduced Aβ burdens in the brains of Aβ-vaccinated 3xTg-AD mice. Additionally, we examined brain glucose metabolism using positron emission tomography with 18F-2 fluoro-2-deoxy-d-glucose. Cerebral glucose uptake was considerably higher in the brains of Aβ-vaccinated 3xTg-AD mice that received bvPLA2 than those that did not. The present study suggests that the modulation of Treg populations via bvPLA2 treatment may be a new therapeutic approach to attenuate the progression of AD in conjunction with Aβ vaccination therapy without an adverse inflammatory response. |
| Databáze: | OpenAIRE |
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