Department of Neuroregeneration
Assoc. Prof. Pavla Jendelová, PhD
The role of sulfation epitopes of brain extracellular matrix in aging and neurodegeneration
Jiří Ružička, PhD
This PhD project aims to understand the role of Chondroitin sulphate transferase 11 (Chst11) in brain extracellular matrix (ECM), and particularly perineuronal nets (PNNs), in aging and neurodegeneration. The project follows a Chst11 knock out study (Chst11ko) in young mice.
Chondroitin sulphate proteoglycan, sulphated at the C4 epitope (in majority by Chst11), form more rigid ECM in comparison with other epitopes. This leads to a less plastic state, with lower probability of synapse formation and decreased mobility of receptors and ion channels, especially in PNN+ neurons. A major increase of C4 sulfation is observed in aging, when it dominates over other more plastic forms. According to the latest research, this could be one of the reasons for cognitive decline in the elderly population.
Using Chst11ko mice we will monitor behavioral changes in aging or tauopathy mice, with the main focus being on short or long-term memory and cognitive flexibility. Moreover, sociability, anxiety and general locomotor function will be measured. Structures of ECM/PNNs will be monitored using biochemical and immunohistochemical analysis. The changes in synaptic connectivity and activity will be measured using several techniques such as super-resolution microscopy, electrophysiology, or proteomics.
For this position we are seeking a motivated student with an interest in neuroscience. Since the project is based on animal experiments, a positive attitude toward animals is necessary. Additionally, previous experience with behavioral neuroscience would be a great advantage. At least basic knowledge of proteomics, qPCR and microscopy techniques is desirable. English at the level B2/C1 is required.
- Foscarin et al., Brain ageing changes proteoglycan sulfation, rendering perineuronal nets more inhibitory. Aging (Albany NY). 2017 Jun 28;9(6):1607-1622. doi: 10.18632/aging.101256. PMID: 28657900; PMCID: PMC5509459.
- Yang et al., Chondroitin 6-sulphate is required for neuroplasticity and memory in ageing. Mol Psychiatry. 2021 Jul 16. doi: 10.1038/s41380-021-01208-9. Epub ahead of print. PMID: 34272488.
- Yang et al., Antibody recognizing 4-sulfated chondroitin sulfate proteoglycans restores memory in tauopathy-induced neurodegeneration. Neurobiol Aging. 2017 Nov;59:197-209. doi: 10.1016/j.neurobiolaging.2017.08.002. Epub 2017 Aug 9. PMID: 28890301.
- Ruzicka et al., PNNs affecting memory retention after synapse withdrawal. Preprint: https://www.biorxiv.org/content/10.1101/2021.04.13.439599v1