In the brain, nerve cells form circuits which are re-modelled by life experience, allowing us to learn and remember. The nerve fibres that make up these circuits are insulated by cells called oligodendrocytes, which increase the speed of information transfer. In MS, the immune system causes regions of damage called lesions. In these damaged regions, the insulation is lost, slowing or interrupting the movement of electrical signals within and from the brain. However, it is not known how this loss of insulation influences circuit re-modelling in brain lesions or more generally in the brain regions without lesions. Dr Kalina Makowiecki predicts that insulation loss and lesion formation is not only associated with the slowing of the electrical signal, but with other changes to nerve cells and brain circuit re-modelling that would affect a person’s ability to remember and multitask (cognition). Such changes could underpin the cognitive impairments experienced by most people with MS.
This incubator project is complementary to an ongoing postdoctoral fellowship being carried out by Dr Makowiecki. It specifically focuses on using advanced microscopy imaging to monitor what happens to specific cellular structures that form the electrical connections in the brain when insulation is lost. Various laboratory models of insulation loss will be investigated. This will improve our understanding of whether nerve insulation loss can impact brain circuit connections and therefore impair cognition.
Dr Makowiecki’s work has shown that myelin loss affects the communication between nerve cells in the brain, not only by slowing it down, but by changing the connections and how reliably one neuron responds to another. This change occurs rapidly after inducing myelin loss in two different laboratory models of MS, and may contribute to some of the symptoms in MS, such as memory and concentration problems, as well as depression or anxiety related symptoms. Importantly, the nerve cells change in a way that could make them vulnerable to irreversible damage. Knowledge of the way that brain circuits change because of MS-like processes, particularly myelin loss, is necessary for identifying and developing treatments that prevent disease progression.
Updated: 19 January, 2021
Laboratory research that investigates scientific theories behind the possible causes, disease progression, ways to diagnose and better treat MS.
Research that builds on fundamental scientific research to develop new therapies, medical procedures or diagnostics and advances it closer to the clinic.
Clinical research is the culmination of fundamental and translational research turning those research discoveries into treatments and interventions for people with MS.