Abstract
BACKGROUND: The polarization to different neuroinflammatory phenotypes has been described in early Alzheimer's disease, yet the impact of these phenotypes on amyloid-beta (Aβ) pathology remains unknown. Short-term studies show that induction of an M1 neuroinflammatory phenotype reduces Aβ, but long-term studies have not been performed that track the neuroinflammatory phenotype.
METHODS: Wild-type and APP/PS1 transgenic mice aged 3 to 4 months received a bilateral intracranial injection of adeno-associated viral (AAV) vectors expressing IFNγ or green fluorescent protein in the frontal cortex and hippocampus. Mice were sacrificed 4 or 6 months post-injection. ELISA measurements were used for IFNγ protein levels and biochemical levels of Aβ. The neuroinflammatory phenotype was determined through quantitative PCR. Microglia, astrocytes, and Aβ levels were assessed with immunohistochemistry.
RESULTS: AAV expressing IFNγ induced an M1 neuroinflammatory phenotype at 4 months and a mixed phenotype along with an increase in Aβ at 6 months. Microglial staining was increased at 6 months and astrocyte staining was decreased at 4 and 6 months in mice receiving AAV expressing IFNγ.
CONCLUSIONS: Expression of IFNγ through AAV successfully induced an M1 phenotype at 4 months that transitioned to a mixed phenotype by 6 months. This transition also appeared with an increase in amyloid burden suggesting that a mixed phenotype, or enhanced expression of M2a and M2c markers, could contribute to increasing amyloid burden and disease progression.
Document Type
Article
Publication Date
7-25-2014
Digital Object Identifier (DOI)
http://dx.doi.org/10.1186/1742-2094-11-127
Repository Citation
Weekman, Erica M.; Sudduth, Tiffany L.; Abner, Erin L.; Popa, Gabriel J.; Mendenhall, Michael D.; Brothers, Holly M.; Braun, Kaitlyn; Greenstein, Abigail; and Wilcock, Donna M., "Transition from an M1 to a Mixed Neuroinflammatory Phenotype Increases Amyloid Deposition in APP/PS1 Transgenic Mice" (2014). Sanders-Brown Center on Aging Faculty Publications. 38.
https://uknowledge.uky.edu/sbcoa_facpub/38
Notes/Citation Information
Published in Journal of Neuroinflammation, v. 11, article 127, p. 1-11.
© 2014 Weekman et al.; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.