# p2rx3 Knockout Mice Have Altered Energy Metabolism in Hippocampal Neurons

## TL;DR

This study shows that p2rx3 knockout mice have significant changes in hippocampal neuron energy metabolism, which could help in developing treatments for cognitive disorders.

## Contribution

The study introduces p2rx3 knockout mice as a novel model for investigating brain energy metabolism and cognitive dysfunction.

## Key findings

- p2rx3 knockout mice show increased ATP production and maximum respiration in hippocampal neurons.
- These mice have reduced spare respiratory capacity, glycolysis rate, and glycolytic capacity.
- Mitochondria in knockout mice operate near maximum energy capacity.

## Abstract

The hippocampus is a key component of the brain that is associated with the
formation of longterm memory, the energy metabolism of neurons playing a
pivotal role in its mechanisms. The P2X3 receptor in the hippocampus is
considered an attractive target when searching for novel biologically active
substances that could work to reduce anxiety, epileptic conditions, and improve
cognitive functions. In this work, the intensity of mitochondrial respiration,
the glycolytic capacity, and the energy phenotype of hippocampal neurons were
studied in p2rx3 knockout mice. The p2rx3
knockout mice were engineered by genome editing using the CRISPR/Cas9
system. The primary mixed culture of hippocampal neurons was derived from
two-day-old newborn mice with the p2rx3-/-and
p2rx3+/-genotypes. Mitochondrial respiration was
measured on a Seahorse Bioscience HS mini Cell Metabolism Analyzer (Agilent,
USA) using the appropriate kits for the Mitostress test, glycotest, and energy
phenotype assessment test. The transgenic mice with the
p2rx3-/- genotype were characterized by an aerobic
type of mitochondrial respiration, an increase in ATP production by 84.4%
(p < 0.05), an increase in maximum respiration by 72.3%
(p < 0.05), and a 36% (p < 0.05)
increase in the respiratory reserve. Meanwhile, the spare respiratory capacity
of mitochondria, the rate of glycolysis, and the glycolytic capacity in these
mice were reduced by 36.6, 75.7 and 78.6% (p < 0.05),
respectively. Our findings indicate that mitochondria work at close to maximum
energy capacity. The p2rx3 knockout animals are a unique model
for the search for pharmacological targets that can help correct the energy
metabolism of brain cells and eliminate cognitive dysfunctions.