How does nerve cell insulation affect memory in MS?

Dr Kalina Makowiecki

Menzies Institute for Medical Research, TAS

| Better treatments | Neurobiology | Fellowship | 2020 | Investigator Led Research |
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Summary

In the brain, nerve cells form circuits which are remodelled by life experience, allowing us to learn and remember things. The nerve fibres that make up these circuits are insulated by a coating or “sheath” made of a fatty substance known as myelin, which increases the speed of information transfer. In MS, the immune system attacks the myelin sheath causing loss of myelin (or “demyelination”) in regions of damage called lesions. In these demyelinated 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 remodeling 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 remodeling that would affect a person’s ability to remember things and to multitask (both are elements of cognition). Such changes could underpin the cognitive impairments experienced by many people with MS.

This project aims to understand whether insulation loss, and the slowing of communication between nerve cells in a brain circuit, can impact brain circuit connections. Knowledge of the cellular changes that occur to brain circuits as a result of MS-like pathology is necessary to overcome debilitating symptoms such as cognitive impairment and fatigue.

Progress to Date

This research study had 3 major aims: to investigate the impact of myelin loss, to determine if demyelination alters the connection circuits in the brain and to examine the impact of demyelination and remyelination (myelin repair) in the brain.

Dr Makiowiecki and her team have commenced the first aim of the study and have collected the brain tissue required to perform the analysis on myelin loss. Work has also begun on the second aim of the study, with the development of demyelination laboratory models and the completion of electrical recordings. The third aim of the study has been delayed because of the COVID-19 pandemic, but initial training has been completed and this work is expected to commence in mid-2021.

Initial findings from the study have shown that myelin loss changes the way that neurons are connected and how they communicate within a circuit. Such changes could affect a person’s ability to remember things and multi-task, potentially leading to some of the cognitive changes we see in MS. By understanding these pathways better, treatments may be developed to help overcome some of the most debilitating and hard to treat symptoms of MS - cognitive impairment and fatigue. Dr Makiowiecki will explore these concepts further over the coming year, with plans to submit a journal article detailing the initial findings in 2021.

Updated: 31st May 2021

Updated: 21 January, 2020

Stages of the research process

Fundamental laboratory
Research

Laboratory research that investigates scientific theories behind the possible causes, disease progression, ways to diagnose and better treat MS.

Lab to clinic timeline: 10+ years
Translational
Research

Research that builds on fundamental scientific research to develop new therapies, medical procedures or diagnostics and advances it closer to the clinic.

Lab to clinic timeline: 5+ years
Clinical Studies
and Clinical Trials

Clinical research is the culmination of fundamental and translational research turning those research discoveries into treatments and interventions for people with MS.

Lab to clinic timeline: 1-5 years

Investigator

  • Dr Kalina Makowiecki

Grant Awarded

  • Postdoctoral Fellowship

Total Funding

  • $180,000

Duration

  • 3 years over 2020 - 2022

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Dr Wolfgang Marx

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How does nerve cell insulation affect memory in MS?