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Updated: May 20, 2025
Two-vessel Occlusion Mouse Model of Cerebral Ischemia-reperfusion
Published on: March 1, 2019
Temporal mRNA Expression of Purinergic P2 Receptors in the Brain Following Cerebral Ischemia and Reperfusion:
Siva Reddy Challa1, Hunter Levingston1, Casimir A Fornal1
1Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine Peoria, Peoria, IL 61605, USA.
Abstract:
Purinergic P2 receptors are crucial in energy utilization and cellular signaling, making them key targets for stroke therapies. This study examines the temporal mRNA expression of all P2 receptors in rats and mice. Both species exhibited a common subset of P2X and P2Y receptors with elevated expression following cerebral ischemia and reperfusion (I/R), highlighting conserved mechanisms across these species. The receptors with upregulated expression in both species were P2X3, P2X4, P2X7, P2Y2, and P2Y6. While these similarities were observed, notable differences in receptor expression emerged between rats and mice. Rats exhibited a broader receptor profile, with five additional receptors (P2X1, P2Y1, P2Y12, P2Y13, and P2Y14) significantly upregulated compared to only two receptors (P2X2 and P2Y4) in mice, highlighting species-specific regulation of receptor expression distinct from the shared receptors. Following cerebral I/R, P2Y12 was the most upregulated receptor in rats, while P2Y2 was the most upregulated in mice. These findings reveal both conserved and species-specific changes in P2 receptor expression following cerebral I/R. Targeting purinergic receptors, particularly those conserved and upregulated in response to stroke, may represent a promising therapeutic approach.
Insights
Purinergic receptors are vital for cellular signaling and stroke therapy targets. This study reveals shared and distinct P2 receptor changes in rats and mice after stroke, offering insights for new treatments.
Area of Science:
- Neuroscience
- Molecular Biology
- Pharmacology
Background:
- Purinergic P2 receptors play critical roles in cellular signaling and energy metabolism.
- These receptors are recognized as significant therapeutic targets for stroke interventions.
Purpose of the Study:
- To investigate the temporal mRNA expression patterns of all P2 receptors in rats and mice following cerebral ischemia and reperfusion (I/R).
- To identify conserved and species-specific changes in P2 receptor expression in response to ischemic stroke.
Main Methods:
- Quantitative analysis of mRNA expression levels for all known P2X and P2Y receptors.
- Comparative study utilizing rat and mouse models of cerebral ischemia and reperfusion.
Main Results:
- Both rats and mice showed upregulated expression of common P2 receptors (P2X3, P2X4, P2X7, P2Y2, P2Y6) after I/R.
- Rats displayed a broader upregulation profile, including P2X1, P2Y1, P2Y12, P2Y13, and P2Y14, while mice showed upregulation of P2X2 and P2Y4.
- P2Y12 was most upregulated in rats, and P2Y2 was most upregulated in mice following I/R.
Conclusions:
- Cerebral I/R induces both conserved and species-specific alterations in P2 receptor mRNA expression.
- Targeting conserved, upregulated purinergic receptors presents a promising avenue for developing novel stroke therapies.
