The Imbalanced Expression of Adenosine Receptors in an Epilepsy Model Corrected Using Targeted Mesenchymal Stem Cell Transplantation
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Adenosine inhibits epileptic episodes by interacting with G-protein-coupled receptors. This study examined the mechanism by which the inhibitory effect of adenosine becomes impaired during epileptogenesis. Dynamic changes in adenosine A1 receptors (A1Rs) and A2a receptors (A2aRs) were investigated in a kindling model of epilepsy. RT-PCR, Western blotting, and immunofluorescence results indicated that expression of A1Rs was increased in the hippocampus 24 h after kindling, but progressively decreased 1 and 6 months after kindling. Opposite changes were seen in the expression of A2aRs. This bidirectional change resulted in an imbalance between A1Rs and A2aRs and dysregulation of the adenosine system. Autologous mesenchymal stem cell (MSC) transplantation was used to correct this disorder and avoid side effects of systematic adenosine therapy. Paramagnetic iron oxide particles were used to mark and track the MSCs in vivo using MRI. The results indicated that the transplanted cells migrated along the callosum and settled at the ependymal layer. The MSCs displayed a relatively long survival time, at least 3 months. The improved AR expression and EEG findings suggested that MSC transplantation was a potentially effective means of treating refractory epilepsy.
KeywordsAdenosine receptors Adenosine kinase Mesenchymal stem cells Epilepsy Transplantation
This work was supported by the National Natural Science Foundation of China (81201006), Natural Science Foundation of Hubei Province (2011CDB201) and Science and Technology Research Plan Project of Wuhan City (201161038339-02).
Conflict of Interest
The authors declare that there were no conflicts of interest for any of the participating authors.
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