Speaker
Description
Rett syndrome is a neurodevelopmental disorder in which the involvement of astrocytes is recognized. Previous work from our laboratory underlined how synaptotoxic factors, such as IL-6, aberrantly expressed by MEPC2 knock-out astrocytes lead to detrimental effects on the synapses in development. Moreover, astrocyte role during development is to provide synaptotrophic factors which could be lacking in diseased MECP2 null or heterozygous environment. With cholesterol being one of the most important synaptogenic factors produced in central nervous system only by astrocytes we focused our attention on its production and distribution among the cell types involved. In our study we were unable to found differences in secreted cholesterol in the medium of co-cultured astrocytes and neurons thus indicating that, if impaired, a different cholesterol delivery mechanism is involved. Nonetheless, we found deregulated gene expression of cholesterol biosynthetic and trafficking pathway in MECP2-null astrocytes. Starting from the hypothesis that cholesterol flow from astrocytes to developing neurons is impaired in Rett syndrome, we are investigating its effect on synaptic compartment in terms of structure and synaptic maturity taking advantage of hiPSC-derived neurons. If proven to be the case that synaptic abnormalities are due to misregulated cholesterol synthesis or delivery our aim would be to evaluate the same results in an in vivo model as a preclinical validation for a feasible mechanism for therapeutic intervention.
| Author(s) | F. Biella, F. M. Postogna, N. Giancroce, O. M. Roggero, N. Landsberger, A. Frasca. |
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| Affiliation(s) | University of Milan |
