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Ultrasound Stimulation Modulates Microglia M1/M2 Polarization and Affects Hippocampal Proteomic Changes in a Mouse
Xinliang Lu1,2, Wenxian Sun1, Li Leng2
1Department of Neurology, Xuan Wu Hospital, Capital Medical University, Beijing, China.
Background:
The effectiveness of ultrasound stimulation in treating Alzheimer's disease (AD) has been reported in previous studies, but the underlying mechanisms remain unclear. This study investigated the effects of ultrasound stimulation on the proportion and function of microglia of different phenotypes, as well as on the levels of inflammatory factors. Additionally, it revealed the alterations in proteomic molecules in the mouse hippocampus following ultrasound stimulation treatment, aiming to uncover potential new molecular mechanisms.
Methods:
Ultrasound stimulation was used to stimulate the hippocampus for 30 min per day for 5 days in the ultrasound stimulation-treated group. Amyloid plaque deposition was measured using immunofluorescence staining. M1 and M2 type microglia were labeled using immunofluorescent double staining, and the ratio was calculated. The levels of Aβ42, IL-10, and TNF-α were determined using ELISA kits. The quantitative proteomics method was employed to explore molecular changes in hippocampal proteins.
Results:
Ultrasound stimulation treatment reduced the average fluorescence intensity of amyloid plaques and the concentration of Aβ42. Compared to the AD group, ultrasound stimulation resulted in a 14% reduction in the proportion of M1 microglia and a 12% increase in the proportion of M2 microglia. The concentration of the anti-inflammatory factor IL-10 was significantly increased in the ultrasound stimulation-treated group. Proteomics analysis revealed 753 differentially expressed proteins between the ultrasound stimulation-treated and AD groups, with most being enriched in the oxidative phosphorylation pathway of mitochondria. Additionally, the activity of cytochrome c oxidase, involved in oxidative phosphorylation, was increased after ultrasound stimulation treatment.
Conclusions:
Ultrasound stimulation affects microglial polarization, reduces amyloid plaque load, and enhances levels of anti-inflammatory factors in APP/PS1 mice. Proteomics analysis reveals molecular changes in hippocampal proteins after ultrasound stimulation treatment. The mechanism behind ultrasound stimulation-induced modulation of microglial polarization may be related to changes in mitochondrial oxidative phosphorylation.
Insights
Ultrasound stimulation therapy reduces Alzheimer's disease plaques and inflammation by shifting microglia balance and enhancing mitochondrial function. This novel approach offers a potential new mechanism for Alzheimer's treatment.
Area of Science:
- Neuroscience
- Biomedical Engineering
- Immunology
Background:
- Alzheimer's disease (AD) pathogenesis involves amyloid plaques and neuroinflammation.
- Microglial phenotypes (M1/M2) play crucial roles in AD progression.
- Underlying mechanisms of ultrasound stimulation for AD remain unclear.
Purpose of the Study:
- Investigate ultrasound stimulation effects on microglial phenotypes in AD.
- Assess changes in inflammatory factors and proteomic profiles post-ultrasound treatment.
- Uncover novel molecular mechanisms of ultrasound therapy in an AD mouse model.
Main Methods:
- Daily ultrasound stimulation applied to the hippocampus of APP/PS1 mice.
- Amyloid plaque load quantified using immunofluorescence.
- Microglial M1/M2 phenotypes and inflammatory markers (Aβ42, IL-10, TNF-α) measured.
- Quantitative proteomics analyzed hippocampal protein alterations.
Main Results:
- Ultrasound stimulation decreased amyloid plaque intensity and Aβ42 levels.
- Significant shift in microglia: 14% decrease in M1, 12% increase in M2.
- Elevated anti-inflammatory IL-10 levels observed.
- Proteomics identified 753 differentially expressed proteins, enriched in mitochondrial oxidative phosphorylation.
Conclusions:
- Ultrasound stimulation modulates microglial polarization, reduces amyloid burden, and increases anti-inflammatory factors in AD mice.
- Proteomic analysis reveals significant hippocampal molecular changes.
- Mechanism may involve enhanced mitochondrial oxidative phosphorylation influencing microglial polarization.
