Abstract
Recent studies indicate that overexpression of adiponectin (APN) could attenuate ischemic brain injury. However, the mechanism of APN effect remains unclear. In this study, we investigated the cellular mechanisms of APN action during cerebral ischemia. Adult mice (n=120) received an intracerebral injection of adeno-associated viral vector carrying the APN gene (AAV-APN). The mice were subjected to a transient ispilateral middle cerebral artery occlusion (tMCAO) after 7-day AAV-APN gene transfer. Cortical atrophy volume, neurological function, microvessels counts, phospho-AMPK and downstream angiogenic factor vascular endothelial growth factor (VEGF) were examined. Overexpression of APN was observed in the mouse brain following AAV-APN gene transfer. Cortical atrophy volume was attenuated in the AAV-APN-transduced mice compared with the AAV-GFP and saline-treated mice (7.9±0.6%, 19.8±0.3% and 20.3±1.1%, respectively, P<0.05), with significant improvement in neurological function and an increased number of microvessels (199±5 vs 151±4 and 148±4 mm–2, P<0.01). Furthermore, the expression of phospho-AMPK and VEGF were increased in the AAV-APN-transduced compared with the control mice (P<0.01), whereas inhibiting phospho-AMPK, reducing VEGF expression and attenuating the effect of APN on brain atrophy and angiogenesis (P<0.01). APN overexpression attenuates ischemia-induced brain atrophy and has improvement in neurological function. The consequence is related to promotion of focal angiogenesis. The AMPK signaling pathway has an important role in upregulating angiogenic factor VEGF.
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Acknowledgements
This study was supported by the 973 Program 2011CB504405 (GYY, YW), the National Natural Science Foundation of China Project #30973097 (GYY), the Young Scientists Fund of the National Natural Science Foundation of China Project # 81100633 (LHS) and a grant from Shanghai Municipal Health Bureau #2010090 (LHS). We thank Ms Karena Shun and Yan Wang for their editorial assistance and staffs of the Neuroscience and Neuroengineering Center for their collaborative support.
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Shen, L., Miao, J., Yuan, F. et al. Overexpression of adiponectin promotes focal angiogenesis in the mouse brain following middle cerebral artery occlusion. Gene Ther 20, 93–101 (2013). https://doi.org/10.1038/gt.2012.7
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DOI: https://doi.org/10.1038/gt.2012.7
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