A recent study reveals the motives behind the decreased brain plasticity of patients suffering from Alzheimer’s and Parkinson’s disease. The study also links the decreased plasticity to diabetes and insulin resistance. The study spanned over a period of 5 years and was conducted in order to understand the way stem cells begin and end their migration inside the brain.
The results of the study surfaced valuable information on the connectivity between brain cells. Professor Maurice Curtis is the main author of the study. His collaborators include Dr Hector Monzo, who was responsible for the experiments conducted during the study, Professor Mike Dragunow, Dr Thomas Park, Dr Deidre Jansson and Distinguished Professor Richard Faull. Curtis explains that during the study, his research team has started testing new drugs that would be able to improve the connectivity between neurons through their action on the polysialic acid removal pathway.
Brain stem cells are the immature cells of the brain that migrate towards different areas of the brain and differentiate into neurons. After reaching their destination, the stem cells differentiate into neurons, which must create dendrites in order to connect with other neurons. The brain circuits of the brain are formed through the connection of numerous neurons. However, the adult brain contains a substance known as extracellular matrix, which fills up the space between the brain cells. The extracellular matrix found inside the brain is rigid and makes the migration of new stem cells difficult.
Despite this rigid extracellular matrix, stem cells can still migrate through the brain because of a special compound known as polysialic acid-neural cell adhesion molecule. This compound binds itself to the surface of each stem cell allowing the stem cell to migrate easily, while also reducing the cellular energy consumption. When the stem cell reaches its destination, the compound is removed from its cellular membrane and the stem cells remains in place, differentiates and starts to build its dendrites.
According to professor Curtis, this process has been known for approximately 20 years. However, there has been very little information regarding the regulation and control of the process. The current study sheds light on the process and what happens to the polysialic acid molecule after it is no longer needed by the stem cell. The research team has been studying the process for the past 5 years, reaching the conclusion that the polysialic acid molecule is internalized after two very specific cues.
The first cue comes from collagen, which is one of the components of the rigid extracellular matrix. The second cue comes from a gaseous compound known as nitric oxide. Furthermore, the research team discovered that the process of internalization is inhibited by increased levels of insulin and insulin-like growth factor 1. Curtis affirms that the most important key to their breakthrough was determining that in order to understand the process through which the polysialic acid molecule binds to the cell membrane, they first had to find a way to stop the process.
Researchers determined that higher levels of insulin were responsible for inhibiting the removal of the polysialic acid molecules, thus blocking the formation of synapses between the newly formed neuron and other nearby brain cells. They affirm that this discovery could hold important information about why the brains of patients suffering from Alzheimer’s and Parkinson’s disease have a diminished level of plasticity.