β-Asarone improves learning and memory in Aβ1-42-induced Alzheimer’s disease rats by regulating PINK1-Parkin-mediated mitophagy

Abstract

Alzheimer’s disease (AD) is a chronic neurodegenerative disease that is characterized by the extracellular accumulation of β-amyloid (Aβ). Many studies have shown a close relationship between autophagy and the formation of Aβ. As AD develops and progresses, mitophagy diminishes insoluble Aβ, and mitochondrial dysfunction seems to be a determining factor in the pathogenesis of AD. In our previous study, we showed that β-asarone pharmacological effects in APP/PS1 transgenic mice, reducing Aβ expression. However, the specific mechanism of this effect remains unclear. In this study, AD model rats induced by intracerebroventricular injection of Aβ1-42 were randomly divided into nine groups, and medical intervention was applied to the animals for 30 days. Subsequently, spatial learning and memory were evaluated by the water maze test. Bcl-2 levels in the hippocampus were determined by western blotting (WB). The protein expression of Aβ1-42, Beclin-1, p62, PINK1, and Parkin was assessed by WB and immunohistochemistry (IHC). The data showed that after β-asarone treatment, the learning and memory of the AD rats were clearly improved compared with those of the model group. Moreover, β-asarone decreased Aβ1-42, Bcl-2, and p62 levels but increased Beclin-1 levels compared with those in the model group. In addition, we treated a group of rats with CsA to inhibit mitophagy. β-Asarone increased PINK1 and Parkin expression compared with that in the model group. The results showed that β-asarone can improve the learning and memory of rats with Aβ1-42-induced AD by effectively promoting PINK1-Parkin-mediated mitophagy. Taken together, these results suggest that β-asarone may have the capacity to become a pharmaceutical agent for the treatment of AD in the future.

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Acknowledgements

This work was supported by the China National Natural Science Foundation Grant No.81903971.

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Correspondence to Yongqi Fang.

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Han, Y., Wang, N., Kang, J. et al. β-Asarone improves learning and memory in Aβ1-42-induced Alzheimer’s disease rats by regulating PINK1-Parkin-mediated mitophagy. Metab Brain Dis (2020). https://doi.org/10.1007/s11011-020-00587-2

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Keywords

  • Mitophagy
  • Alzheimer’s disease
  • PINK1/Parkin
  • β-Asarone