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Published on: March 16, 2016
[Different doses transplanted microglia effect on β-amyloid protein in rat Alzheimer's models]
Yue Huang1, Xiu-Hua Ren, Shan-Feng Zhang
1Department of Neurology, Henan Provincial People's Hospital, Zhengzhou 450003, China.
Objective:
To explore the effects of different doses of transplanted microglia (MG) on β-amyloid protein (Aβ) in rat brain model of Alzheimer's disease (AD).
Methods:
A total of 60 SD rats were randomly divided into experimental group and control group. The experimental group was injected with Aβ-42 and the control group saline in hippocampus. At Day 3, different doses of continuously expressed enhanced green fluorescent protein (EGFP) microglial cells cultured in vitro were injected into the rats via carotid artery. At Day 3 post-injection, Aβ was labeled by immunofluorescent method. And the expressions of EGFP microglia and Aβ were detected in hippocampus by fluorescence. The relative brain expression of β-amyloid precursor protein (APP) mRNA was analyzed by RT-PCR (reverse transcription-polymerase chain reaction).
Results:
The mean fluorescent intensity of EGFP was significantly higher in each experimental group (5.62 ± 0.61, 8.85 ± 0.33, 10.24 ± 0.45, 11.26 ± 0.37, 12.75 ± 0.65) than the control group (2.22 ± 0.32, all P < 0.05); Fluorescent immunohistochemistry showed that the mean fluorescent intensity of Aβ in the 4×10(6) dose group (9.53 ± 0.23) and the 12×10(6) dose group (8.32 ± 0.46) were significantly higher than that in the 8×10(6) dose group (4.56 ± 0.13, both P < 0.05); The fluorescent regions had partial consistence of EGFP and Aβ; RT-PCR (reverse transcription-polymerase chain reaction) results showed that the relative expressions of APP mRNA in the 4×10(6) dose group (1.83 ± 0.22) and the 12×10(6) dose group (1.94 ± 0.28) were significantly higher than that in the 8×10(6) dose group (0.43 ± 0.12, both P < 0.05).
Conclusion:
Aβ has the chemotactic role of MG. MG may swallow Aβ protein partially. But a high dose of MG also accelerates the formation of Aβ.
Insights
Transplanted microglia (MG) can partially clear amyloid-beta (Aβ) in an Alzheimer
Area of Science:
- Neuroscience
- Immunology
- Biomedical Research
Background:
- Alzheimer's disease (AD) is characterized by the accumulation of β-amyloid protein (Aβ) in the brain.
- Microglia (MG) are the resident immune cells of the central nervous system and play a role in neuroinflammation and Aβ clearance.
- Investigating the therapeutic potential of transplanted microglia in AD models is crucial for developing novel treatment strategies.
Purpose of the Study:
- To evaluate the impact of varying doses of transplanted microglia on Aβ deposition in a rat model of Alzheimer's disease.
- To determine the relationship between microglia dose, Aβ clearance, and the expression of amyloid precursor protein (APP) mRNA.
Main Methods:
- Sixty Sprague-Dawley rats were induced with Aβ-42 or saline to create an AD model.
- Enhanced green fluorescent protein (EGFP)-labeled microglia were transplanted via carotid artery at different doses.
- Aβ and EGFP expression were quantified using immunofluorescence; APP mRNA levels were analyzed by RT-PCR.
Main Results:
- Transplanted EGFP microglia were successfully detected in the hippocampus, with higher fluorescence intensity correlating with increased doses.
- Aβ levels were significantly higher in rats receiving 4x10^6 and 12x10^6 microglia doses compared to the 8x10^6 dose.
- Partial co-localization of EGFP and Aβ was observed, suggesting microglia-mediated Aβ interaction; APP mRNA levels were elevated at higher microglia doses.
Conclusions:
- Microglia exhibit chemotaxis towards Aβ, indicating a potential role in Aβ aggregation.
- While microglia may partially phagocytose Aβ, high doses appear to exacerbate Aβ formation and APP mRNA expression.
- The dose-dependent effects of transplanted microglia highlight the complexity of their role in AD pathogenesis and suggest a need for careful dose optimization in therapeutic strategies.

