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p2rx3 Knockout Mice Have Altered Energy Metabolism in Hippocampal Neurons
A S Zelentsova1, M V Pokrovskii1, E A Patrakhanov1
1Belgorod State National Research University, Belgorod, 308015 Russia.
Acta Naturae
|October 22, 2025
Summary
Mice lacking the P2X3 receptor show altered brain cell energy metabolism, with increased mitochondrial respiration and ATP production. This discovery offers a new model for targeting cognitive dysfunction.
Area of Science:
- Neuroscience
- Cellular Metabolism
- Genetics
Background:
- The hippocampus is crucial for memory formation, with neuronal energy metabolism playing a key role.
- The P2X3 receptor in the hippocampus is a potential target for treating anxiety, epilepsy, and cognitive impairments.
Purpose of the Study:
- To investigate the impact of P2X3 receptor knockout on hippocampal neuron energy metabolism.
- To characterize the mitochondrial respiration, glycolytic capacity, and energy phenotype in p2rx3 knockout mice.
Main Methods:
- Generation of p2rx3 knockout mice using CRISPR/Cas9 genome editing.
- Primary mixed culture of hippocampal neurons derived from p2rx3-/- and p2rx3+/- mice.
- Measurement of mitochondrial respiration and glycolysis using a Seahorse XF Analyzer.
Main Results:
- p2rx3 knockout mice exhibited an aerobic mitochondrial respiration pattern.
- Significant increases in ATP production (84.4%), maximum respiration (72.3%), and respiratory reserve (36%) were observed.
- Reductions in spare respiratory capacity (36.6%), glycolysis rate (75.7%), and glycolytic capacity (78.6%) were noted.
Conclusions:
- Hippocampal neurons in p2rx3 knockout mice operate near their maximum energy capacity.
- These mice represent a valuable model for identifying pharmacological targets to correct brain cell energy metabolism and cognitive deficits.
