Abstract
AMP-activated protein kinase (AMPK) is a regulator of cellular energy metabolism. Long-term use of metformin, an AMPK activator, was previously reported to be neuroprotective, as it promotes behavioral improvement and angiogenesis following an acute ischemic injury of the brain. However, only a few studies have demonstrated the role of AMPK in alleviating chronic cerebral ischemia (CCI) in mice models in the long-term (over 3 months). Therefore, we established a mouse model of CCI via bilateral carotid artery stenosis (BCAS) to explore the effect of AMPK on CCI. We used four groups of 3-month-old male C57BL/6 mice labeled as Sham, BCAS, BCAS + metformin treatment (BCAS + Met) and BCAS + AMPKα2 gene knockout (BCAS + KO). Three months after BCAS, we measured the AMPK protein expression, spatial learning and memory, Nissl bodies, cell apoptosis, astrocyte activation, and oligodendrocyte maturation. Additionally, we observed the brain tissues for changes in cell morphology. We observed that mice in the BCAS group had impaired spatial learning and memory compared with those in the sham group. The brain tissues of mice with CCI injury showed altered cell morphology, fewer Nissl bodies, cerebral cells apoptosis, and astrocyte activation. Interestingly, compared with mice from the BCAS group, the brains of mice from BCAS + Met group suffered lesser damage, whereas those of mice from the BCAS + KO group suffered more damage. The activation of AMPK, especially AMPKα2, plays a neuroprotective role during CCI in a mouse model of BCAS.
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Data Availability
The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request. The materials involved in the current study are available from commercial sources.
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Acknowledgements
This work was partly supported by Grant No. 82071277(BC), and 81571133 (BC) of Natural Science Foundation of China, Grant No. 2018Y9084 (BC) Joint Funds for the innovation of science and Technology, Fujian province, and Grant No. 2019J01450 (BC) of Fujian Provincial Natural Science Foundation.
Funding
This work was partly supported by Grant No. 82071277(BC), and 81571133 (BC) of Natural Science Foundation of China, Grant No. 2018Y9084 (BC) Joint Funds for the innovation of science and Technology, Fujian province, and Grant No. 2019J01450 (BC) of Fujian Provincial Natural Science Foundation.
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BC, YZ, and YZ participated in the design of this study. WX and YZ both performed the statistical analysis. YZ carried out the study and collected important background information. WX drafted the manuscript. All authors read and approved the final manuscript.
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Xie, W., Zeng, Y., Zheng, Y. et al. Activated AMPK Protects Against Chronic Cerebral Ischemia in Bilateral Carotid Artery Stenosis Mice. Cell Mol Neurobiol 43, 2325–2335 (2023). https://doi.org/10.1007/s10571-022-01312-6
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DOI: https://doi.org/10.1007/s10571-022-01312-6