Determining the role of IL-4 induced neuroinflammation in microglial activity and amyloid-β using BV2 microglial cells and APP/PS1 transgenic mice

Autor: Clare H Latta, Erica M. Weekman, Tiffany L. Sudduth, Kaitlyn Braun, Gabriel J. Popa, Floracita Gonzalez-Oregon, Erin L. Abner, Michael D. Mendenhall, Donna M. Wilcock
Rok vydání: 2015
Předmět:
Time Factors
Beta-amyloid
Amyloid beta-Protein Precursor
Mice
0302 clinical medicine
Transduction
Genetic
Cell Line
Transformed
0303 health sciences
Microglia
General Neuroscience
3. Good health
Cell biology
medicine.anatomical_structure
Neurology
Cytokines
Encephalitis
medicine.symptom
Alzheimer’s disease
Genetically modified mouse
Green Fluorescent Proteins
Immunology
Mice
Transgenic
Inflammation
Neuroprotection
03 medical and health sciences
Cellular and Molecular Neuroscience
Immune system
Alzheimer Disease
In vivo
Glial Fibrillary Acidic Protein
Presenilin-1
medicine
Animals
Humans
Neuroinflammation
Interleukin 4
030304 developmental biology
Amyloid beta-Peptides
business.industry
Research
Mice
Inbred C57BL
Disease Models
Animal
Gene Expression Regulation
Mutation
Interleukin-4
business
030217 neurology & neurosurgery
Zdroj: Journal of Neuroinflammation
ISSN: 1742-2094
Popis: Background Microglia are considered the resident immune cells of the central nervous system (CNS). In response to harmful stimuli, an inflammatory reaction ensues in which microglia are activated in a sequenced spectrum of pro- and antiinflammatory phenotypes that are akin to the well-characterized polarization states of peripheral macrophages. A “classically” activated M1 phenotype is known to eradicate toxicity. The transition to an “alternatively” activated M2 phenotype encompasses neuroprotection and repair. In recent years, inflammation has been considered an accompanying pathology in response to the accumulation of extracellular amyloid-β (Aβ) in Alzheimer’s disease (AD). This study aimed to drive an M2a-biased immune phenotype with IL-4 in vitro and in vivo and to determine the subsequent effects on microglial activation and Aβ pathology. Methods In vitro, exogenous IL-4 was applied to BV2 microglial cell cultures to evaluate the temporal progression of microglial responses. In vivo, intracranial injections of an adeno-associate-virus (AAV) viral vector were performed to assess long-term expression of IL-4 in the frontal cortex and hippocampus of Aβ-depositing, APP/PS1 transgenic mice. Quantitative real-time PCR was used to assess the fold change in expression of biomarkers representing each of the microglial phenotypes in both the animal tissue and the BV2 cells. ELISAs quantified IL-4 expression and Aβ levels. Histological staining permitted quantification of microglial and astrocytic activity. Results Both in vitro and in vivo models showed an enhanced M2a phenotype, and the in vivo model revealed a trend toward a decreased trend in Aβ deposition. Conclusions In summary, this study offers insight into the therapeutic potential of microglial immune response in AD.
Databáze: OpenAIRE
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