Borges Group - Brain metabolism

Borges lab members

We are interested in morphological, biochemical and functional changes leading to seizures in epilepsy. The long-term goal is to find new and effective treatments for epilepsy that have few side effects. To this end, we are using preclinical models of epilepsy and have implemented clinical trials.

Glucose metabolism is often compromised in brain areas that generate seizures, which can lead to lack of energy. Most of the brain’s energy in neurons and astrocytes is needed for ion balancing and neurotransmission. Thus, lack of fuel can result in increases in extracellular potassium levels and impairments in glutamate handling, which can trigger abnormal excessive neuronal activity and seizure generation.

Our strategy is therefore to find a way to improve energy levels in the brain, with the aim to improve energy levels when glucose metabolism is insufficient.

We have focussed on medium chain triglycerides (MCTs), a type of fat that is sometimes added to medical ketogenic diets for the treatment of epilepsy. We have shown that different MCTs, when added to normal diets, can prevent seizure generation in seizure models. The body metabolises MCTs to two different auxiliary fuel types, namely ketone bodies and medium chain fatty acids. Both of these substances are taken up by the brain. Ketone bodies provide extra fuel to neurons, while medium chain fatty acids are metabolized by astrocytes. There is no competition for the metabolism of these substances, which render MCTs an ideal means to provide extra fuel to both brain cell types. Clinical trials (see Miscellaneous tab) have been initiated by our lab and others to test whether add-on MCT to a normal diet can be used to treat epilepsy.

Ongoing studies are investigating ways to improve glucose and glycogen metabolism.

A new aspect of our research is focusing on proteostasis and microglial metabolic reprogramming, which is led by Dr Liviu-Gabriel Bodea.

  • Metabolic changes in epilepsy
  • New approaches to improve glucose metabolism in epilepsy

For Honours and PhD projects please email Associate Professor Borges.

 

Group Head

Team members

Microglia Metabolic Reprogramming and Proteostasis Research Team

View full list of publications on eSpace

Xu, Weizhi, Neal, Elliott S., Plan, Manuel and Borges, Karin (2022). Glyceryl triacetate feeding in mice increases plasma acetate levels but has no anticonvulsant effects in acute electrical seizure models. Epilepsy & Behavior, 137 (Pt A) 108964, 108964. doi: 10.1016/j.yebeh.2022.108964

Find out more about our diverse range of research interests.