Mitochondria are fundamental subunits of each and every cell that makes up the human body. When mitochondrial dysfunction occurs on a large scale or throughout an entire system, it typically results in low energy levels, cell damage, and eventually cell death if it is not treated. Mitochondria are responsible for the generation of the energy that is necessary for cells to complete their normal and required functions. The heart, liver, muscles, kidneys, and brain are the most common locations in which mitochondrial dysfunction can be found .
In light of the fact that mitochondria play a direct role in neuronal function, and in light of the fact that perioperative neurocognitive illness (PND) is one of the most commonly seasoned and least understood infection rates (especially in elderly sick people), Zhao et al. investigated the specific role that the microtubule antioxidant elamipretide (SS-31) plays in preventing mitochondrial dysfunction as well as synaptic and memory impairment caused by oxidative stress and inflammation.
Elamipretide could offer protection against memory impairment experienced during neuroinflammation, specifically by offering protection against mitochondrial dysfunction and by reducing oxidative stress and inflammatory response in the hippocampus, as hypothesised by Zhao et al. in light of previous research carried out in this particular area.
Before evaluating memory performance and hippocampus-related learning with a battery of open field, Morris water maze (MWM), and fear conditioning tests, the authors of this study randomly assigned mice to one of four treatment groups: a control plus placebo group, a control plus elamipretide group, an LPS plus placebo group, or an LPS plus elamipretide group. Each of these groups received either a placebo injection or an injection of elamipretide
After finishing all of their tests, the authors came to the conclusion that elamipretide:
- Protected the hippocampus from the mitochondrial dysfunction that is caused by LPS by ensuring that acceptable levels of mitochondrial membrane potential (MMP) and adenosine triphosphate assay were maintained (ATP).
- In the hippocampus, there was a decrease in both oxidative stress and the inflammatory response that was generated by LPS (of mice).
- Reduced by a sizeable amount the number of neuronal cells that died within the hippocampus of mice that had been treated with LPS.
- In mice that had been treated with LPS, an increase in both the hippocampus brain-derived neurotrophic factor (BDNF) pathway and synaptic structural complexity was seen.
- LPS treatment was unable to cause a decrease in the number of dendritic spines seen on hippocampal neurons.
Even though LPS treatment resulted in poor learning and memory function in the hippocampus of mice, Zhao et al. came to the conclusion that memory impairment brought on by LPS may be greatly mitigated by the administration of the mitochondria-targeted inhibitor elamipretide. In addition, elamipretide may have the potential to be used as a therapeutic agent in the prevention of damage brought on by oxidative stress and neuroinflammation, both of which are recognised as factors that contribute to PND. In light of these findings, the authors urge additional investigation into the possibility of using mitochondria as a component of a therapeutic approach for patients suffering from PND.