Wellcome Trust Centre For Mitochondrial Research

Inhibitory neurons and mitochondrial disease

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Last month, first year PhD student Elizaveta Olkhova talked to us about her research project that involves dissecting the molecular mechanisms underpinning hyperexcitable neuronal networks in mitochondrial disease. But what does this mean? Read on to find out more. 

Mitochondrial disorders are a group of genetic disorders in which mitochondrial dysfunction results in difficulty generating energy for cells, particularly those with high-energy demands such as brain and muscle.

Neurological symptoms, such as ataxia (problems with balance and coordination), epilepsy, cognitive impairment and stroke-like episodes, are often found in patients with mitochondrial disease. Epilepsy is a common feature which can be debilitating and often challenging to treat. Epilepsy is thought to arise due to abnormal brain wave activities.

Previous studies have shown that inhibitory neurons, an important group of nerve cells that controls the brain rhythm and dampens down excess excitation, requires a lot of energy to maintain their functions. My PhD project aims to explore whether inhibitory neurons are particularly susceptible to mitochondrial dysfunction, resulting in altered brain activity and generation of seizures.

For my project, we have designed a new mouse model in which only the inhibitory neurons (shown in the image) develop mitochondrial dysfunction, while the function of other cells remain unchanged.  We plan to evaluate the growth, behaviour and brain wave activities in these mice with abnormal mitochondrial function, and compare them to the wild-type (‘normal’) mice. We are hoping that this mouse model will allow us to better understand the impact of mitochondrial dysfunction on inhibitory neurons and the development of ataxia and epileptic seizures. To find out whether the mouse model is relevant to human disease, we will also compare the animal data with the post-mortem findings that we learn from patients affected by mitochondrial disease.

One of the most exciting potentials of my study is that we can use this mouse model to screen medications or new compounds that can achieve better seizure control or maintain brain functions before performing drug trials in patients living with mitochondrial disease.

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