Projects / Programmes
Mobility Regulation of Retrieving Secretory Organelles in Astrocytes
| Code |
Science |
Field |
Subfield |
| 3.03.00 |
Medical sciences |
Neurobiology |
|
| Code |
Science |
Field |
| B470 |
Biomedical sciences |
Physiology |
astrocyte, vesicle, recycling, trafficking, glia, intermediate filaments, cytoskeleton, reactive gliosis
Researchers (10)
Organisations (2)
Abstract
For over one hundred years glial cells such as astrocytes were considered to play a subservient role to neurons. However, in the recent decade it became clear that like neurons glial cells exhibit a special form of excitability and are releasing and responding to chemical messengers. Thus, mechanisms of communication between glia and adjacent cells, especially neurons, remain one of the key questions to be addressed.
Communication between cells in the nervous system is largely determined by a delicate balance between uptake and release of substances into/from astrocytes. One of the important mechanisms of substance release from astrocytes is also regulated exocytosis. Astrocytes are recently viewed as a key element in cell-to-cell communication. From this perspective and in view that astrocytes play a role in a number of neurodegenerative diseases and trauma, it is of crucial importance to reveal and understand mecanisms which determine the trafficking of these secretory vesicles from (retrieval) and to the plasma membrane, where substances can be discharged from vesicle lumen into the extracellular space.
Recently the trafficking of retrieving secretory vesicles (peptidergic and glutamatergic) in astrocytes have been observed and evaluated. It was found that in altered physiological conditions their trafficking was substantially changed. This finding is of particular importance, since physiological conditions alter in a number of neurodegenerative diseases and trauma; leading to the development of astrocyte reactivation, which is characterized by a change in the expression of many genes. The consequences of these physiological, as well as morphological changes, remain almost completely unknown. Therefore, extensive efforts are being considered to analyse different subcellular compartments of reactive astrocytes. In particular the role of the cytoskeleton (especially intermediate filaments, IFs), and of proteins playing a role in water transport, since pathological conditions are often associated with cellular and extracellular oedema. Due to highly increased expression of IFs in reactive astrocytes and in view of the finding that trafficking of retrieving vesicles is affected in altered physiological states, it is considered that the retrieving of vesicles is changed also in reactive astrocytes. We hypothesize that substantial upregulation of IFs in neurodegenereative disorders and in trauma may affect the trafficking of exocytotic vesicles and therefore affecting the release of signalling substances and membrane water transport.
Our aim is to evaluate the role of IFs in vesicle recycling in astrocytes by the use of the well established method of genetically manipulated mice without IFs (GFAP-/-Vim-/-). We will study the trafficking of different membrane-bound vesicles in wild-type and genetically manipulated mice; these studies will be extended to experiments on brain slices to compare the results obtained in astrocyte cultures to the cell environment, which more closely resembles the in vivo conditions.
Significance for science
CNS pathologies (disease and trauma) are a serious burden for the patients and society in the EU and worldwide. However, effective treatments are still not available, since the basic biological principles related to these conditions are not accessible to straightforward experimental approaches due to the complexity of the nervous tissue. By studying single cells and cells within tissue slices, the results of our research will importantly contribute to a better understanding of the subcellular processes in the brain cells astrocytes. In particular, this work will reveal the regulation of trafficking of recycling vesicles in astrocytes which contain secretory cargo within the vesicle lumen or carry vesicle membrane associated molecules. The findings of these largely understudied phenomena may lead to potentially new targets / paradigms to be considered in introducing new treatment strategies. Thus as such the proposed work will provide fundamental new insights into cell pathobiology related to trauma, ishaemic stroke and neurodegenerative diseases of the CNS.
Significance for the country
There is no direct impact on economy. However through education process, into which our labortaory is engaged at the undergraduate and postgraduate level, the results of this research will have an impact. Training of young researchers in the research field will augment the human potential in the country and also increase the visibility of the country internationally. Furthemore, the results of this research will help to access the EU and international collaboration within the field of neuron-glia interaction, a theme of research addressed in the calls of The European Comission.
Most important scientific results
Annual report
2008,
2009,
final report,
complete report on dLib.si
Most important socioeconomically and culturally relevant results
Annual report
2008,
2009,
final report,
complete report on dLib.si
