Project description
Plasticity in the brain and spinal cord is controlled by perineuronal networks (PNNs), which contain proteoglycans and surround parvalbumin-positive inhibitory interneurons and motoneurons. Uncoupling of these networks promotes the recovery of function in animal models of spinal cord injury. One potential modulator is 4-methylumbelliferone (4MU), which inhibits hyaluronan (HA) and CSPG synthesis and regulates PNN formation in the nervous system.
Our pilot data show that oral administration of 4MU led to the outgrowth of 5HT+ nerve fibres into the ventral horns and reduced hyaluronan production by astrocytes around the lesion site in rats with chronic spinal cord lesions. In addition, 4MU reduced the glial scar in the chronic phase of spinal cord injury. In this project, building on the applicant’s pilot results, the administration of 4MU will be shortened to the shortest possible time as hyaluronan synthesis is affected throughout the body, including the connective tissue, and animals with regular training once a week will survive long-term and their functional motor improvement will be monitored. It is hypothesised that the newly formed connections enhanced by the rehabilitation will remain at least partially preserved even after temporary inhibition of the hyaluronan synthase ceases.
Candidate profile
M.Sc. in biology, biotechnology or medicine. Ability to work with animals, including surgery and animal testing. We require a cover letter, CV and contacts of two experts who can provide references.
Suggested reading
- Preprint: https://doi.org/10.1101/2023.01.23.525137
- doi: 10.1038/s41598-023-46539-5
- doi: 10.1038/s41598-020-67526-0
