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Microglial activation with reduction in autophagy limits white matter lesions and improves cognitive defects during
Zhao Yang, Nan Zhang, Hanchao Shen
1Department of Neurosurgery, The 476th Hospital of PLA, Fuzhou, Fujian 350025, China. ytt83812280@sina.com.
Abstract:
Microglial activation plays a vital role in the pathogenesis of white matter lesions (WMLs) during chronic cerebral hypo perfusion. Autophagy has been associated with both microglia survival and cell death. Yet, the role of autophagy during microglial activation in chronic cerebral ischemia is still unknown. We used a chronic cerebral hypoperfusion model by permanent stenosis of bilateral common carotid artery in mice to study microglial activation and autophagy. However, the autophagy inhibitor (3-methyladenine) could attenuate microglial autophagic activation, decrease white matter lesions, and improve working memory during chronic cerebral hypoperfusion in mice. In conclusion, chronic cerebral hypoperfusion that leads to microglial activation and autophagy induction exacerbates white matter lesions and cognitive deficits in mice. Our findings represent a potential novel target for chronic cerebral hypoperfusion therapy.
Insights
Chronic cerebral hypoperfusion activates microglia and autophagy, worsening white matter lesions and cognitive deficits. Inhibiting autophagy may offer a therapeutic target for this condition.
Area of Science:
- Neuroscience
- Pathology
- Cell Biology
Background:
- Microglial activation is crucial in white matter lesion (WML) development in chronic cerebral hypoperfusion.
- Autophagy's role in microglial activation during chronic cerebral ischemia remains unclear.
- Understanding this role is vital for developing new therapeutic strategies.
Purpose of the Study:
- To investigate the role of autophagy in microglial activation during chronic cerebral hypoperfusion.
- To determine the impact of modulating autophagy on WMLs and cognitive function in a mouse model.
Main Methods:
- A mouse model of chronic cerebral hypoperfusion was established using permanent stenosis of bilateral common carotid arteries.
- The study examined microglial activation and autophagy markers.
- An autophagy inhibitor, 3-methyladenine, was administered to assess its effects.
Main Results:
- Chronic cerebral hypoperfusion induced microglial activation and autophagy.
- Inhibition of autophagy with 3-methyladenine attenuated microglial autophagic activation.
- Autophagy inhibition led to decreased WMLs and improved working memory.
Conclusions:
- Chronic cerebral hypoperfusion exacerbates WMLs and cognitive deficits through microglial activation and autophagy induction.
- Targeting autophagy presents a potential therapeutic avenue for chronic cerebral hypoperfusion.
- Further research into autophagy modulation could lead to novel treatments.
