The polarization to different neuroinflammatory phenotypes has been described in early Alzheimer’s disease, yet the impact of these phenotypes on amyloid-beta (Abeta) pathology remains unknown. Short-term studies show that induction of an M1 neuroinflammatory phenotype reduces Abeta, 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 IFNgamma or green fluorescent protein in the frontal cortex and hippocampus.
Mice were sacrificed 4 or 6 months post-injection. ELISA measurements were used for IFNgamma protein levels and biochemical levels of Abeta.
The neuroinflammatory phenotype was determined through quantitative PCR. Microglia, astrocytes, and Abeta levels were assessed with immunohistochemistry.
Results:
AAV expressing IFNgamma induced an M1 neuroinflammatory phenotype at 4 months and a mixed phenotype along with an increase in Abeta 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 IFNgamma.
Conclusions:
Expression of IFNgamma 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.
Author: Erica M WeekmanTiffany L SudduthErin L AbnerGabriel J PopaMichael D MendenhallHolly M BrothersKaitlyn BraunAbigail GreensteinDonna M Wilcock
Credits/Source: Journal of Neuroinflammation 2014, 11:127
Published on: 2014-07-25
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