Oligodendrocytes | Neuronetwork

What are oligodendrocytes? 

Oligodendrocytes are specialized cells in the brain that produce myelin, a fatty substance that insulates nerve fibers and helps electrical signals travel quickly. They also support the metabolic needs of nerve cells, providing them with nutrients and energy.  

Why oligodendrocytes and brain health? 

Under normal conditions, oligodendrocytes support neurons by providing them with substrates to meet their energy demands. Recent research suggests that metabolic syndrome (MetS) causes a breakdown in oligodendrocyte function, leading to nerve cell loss and, subsequently, Alzheimer’s disease and Alzheimer’s disease-related dementias (AD/ADRD). Indeed, we found that the ability of oligodendrocytes to provide metabolic support to neurons declines with age in mouse models of MetS. However, our understanding is limited regarding how MetS and the resulting disruptions in oligodendrocyte support for neurons contribute to cognitive problems and diseases such as AD/ADRD.   

Using cell culture and mouse models of MetS, as well as high throughput sequencing techniques and novel bioinformatic approaches, we are investigating oligodendrocyte-neuron metabolic crosstalk to discover and evaluate new therapeutic targets for MetS-associated cognitive impairment and AD/ADRD.  

Key areas: 

Gene expression in oligodendrocytes 

We believe that MetS causes genetic and molecular changes in oligodendrocytes that disrupt their ability to communicate with and metabolically support neurons. We are using novel transcriptomic and bioinformatic techniques to assess changes in gene expression in the hippocampus of mice fed a high-fat diet. This work will help us understand how MetS in midlife disrupts molecular pathways in oligodendrocytes, leading to AD/ADRD in later life.   

Oligodendrocyte-neuron metabolic crosstalk 

Most research has concentrated on how oligodendrocytes help with myelin formation, which insulates nerve fibers. However, there’s growing interest in how these cells also supply energy to neurons. Unfortunately, there’s a lack of well-developed laboratory models to study the detailed mechanics of oligodendrocyte and neuron energy transfer and how MetS affects this interaction.  

To address this limitation, we generated an in vitro model that combines oligodendrocytes and neurons to study how these cells process energy and nutrients. We anticipate that MetS will interfere with the energy exchange between the two types of brain cells, particularly in the transfer of lactate, a key energy source, which will harm the energy-producing abilities of neurons. Through these studies, we aim to understand how the breakdown in energy exchange between these cells contributes to conditions like AD/ADRD.  

Targeting the lactate shuttle 

In the brain, the monocarboxylate transporter 1 (MCT1) protein transports lactate from oligodendrocytes to neurons in a process often called the “lactate shuttle.” We want to understand the role of MCT1 and its potential use as a therapeutic target in MetS and AD/ADRD. To do so, we are comparing two groups of mice fed a high-fat diet: one group with a genetic modification that removes MCT1 in oligodendrocytes and another group without this modification.