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 (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 remodelling in brain lesions, or more generally in the brain regions without lesions.

Dr Kalina Makowiecki predicted 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 remodelling that would affect a person’s ability to remember things and to multitask (both are elements of cognition).

Progress to Date

Dr Kalina Makowiecki has made considerable progress in understanding the effects of myelin loss on neuronal connections, and miscommunication between nerve cells. 

In a laboratory model, experiments involving taking pictures of the brain (imaging) during demyelination and remyelination have been conducted and this phase of the project is expected to be completed mid-2023. Initial analysis suggests that when the myelin starts to disappear (demyelination), the rate of change of certain structures called spines increases. These spines, which are important for communication between nerve cells, are formed more rapidly but also disappear more quickly compared to normal situations. Further imaging and analyses are underway to complete the dataset. The project's positive outcomes are expected to be submitted for publication. 

Dr Kalina Makowiecki has also focused on career development opportunities and the acquisition of new skills. She attended the Australian Course in Advanced Neuroscience (ACAN), which enhanced her skills in measuring electrical signals in the brain (electrophysiology), imaging, and studying how the brain functions as a whole (systems neuroscience). Furthermore, Dr. Makowiecki has honed her project management and mentoring abilities by overseeing the progress of two PhD students and has focused on improving her communication skills to effectively present her research to different audiences. As a result of her efforts, she has successfully presented her findings at several conferences, including the Progress in MS conference, the Myelin Gordon Research Conference, and the Australasian Neuroscience Society Conference. 

Overall, the project provides exciting new insights that may have implications for MS and other neurodegenerative diseases. 

Publications

  • ^Fletcher J; ^Makowiecki K; Cullen CL, Young KM. (2021). Oligodendrogenesis and Myelination Regulate Cortical Development, Plasticity and Circuit Function. Seminars in Cell and Developmental Biology. 118:14-23. ^Equal primary author. 
  • Makowiecki K, Stevens N, Cullen CL, Zarghami A, Nguyen TP; Johnson L, Rodger J, Hinder MR Barnett M, Young KM; Taylor BV. (2022). Safety of low -intensity repetitive transcranial magnetic stimulation for people living with multiple sclerosis: study protocol for a randomised controlled trial. Trials. 23, 626. 

Updated: 31 March 2023

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

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Dr Wolfgang MarxMS Researcher Dr Grant Parnell

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How does nerve cell insulation affect memory in MS?