The brain is plastic and is built for changes in its structure and function. Structural and functional plas- ticity have been the subject of intense investigation, but whether similar phenomena occur also in astro- cytes remains enigmatic. The reason for this noticeable gap of knowledge is that until recently, we lacked microscopy approaches that can provide both a high-resolution image of astrocytic processes and a full description of the morphology of entire astrocytes. Expansion microscopy can challenge this status quo by providing an exciting new way to analyze the structure of astrocytes and the distribution of membrane proteins. The overall objective is to determine how the morphology of astrocytes and the sub-cellular distribution of glutamate transporters changes during the sleep/wake cycle. Our central hy- pothesis is that astrocytic processes move away from excitatory synapses during the sleep phase, al- tering glutamate diffusion and weakening excitatory synaptic transmission in the brain. We plan to test our central hypothesis and attain the objective of this application by pursuing the following specific aims: (1) determine the effect of the sleep/wake cycle on astrocyte morphology; (2) map the molecular distribution of glutamate transporters in astrocytes during the sleep/wake cycle; (3) develop 3D models of glutamate diffusion and excitatory transmission during the sleep/wake cycle. The proposed research is significant because it may generate groundbreaking information on how changes in the structure and function of astrocytes contribute to the onset of neurodegenerative diseases. The proposed research is innovative because it aims to develop a new and comprehensive toolbox to investigate fundamental mechanisms regulating the function of the brain. Ultimately, these findings are expected to have an im- portant positive impact in the delineation of the molecular and cellular mechanisms underlying our cog- nitive abilities during health and disease.
The proposed research is relevant to public health because the discovery of fine structural changes in astrocyte morphology and function is ultimately expected to contribute to the development of novel tools to prevent, delay and possibly cure brain diseases like Alzheimer?s disease. Therefore, the pro- posed research is relevant to the NIH?s mission because it can help lengthen life and reduce the bur- dens of neurodegenerative disease.
| Scimemi, Annalisa (2018) Astrocytes and the Warning Signs of Intracerebral Hemorrhagic Stroke. Neural Plast 2018:7301623 |
| Gavrilov, Nikolay; Golyagina, Inna; Brazhe, Alexey et al. (2018) Astrocytic Coverage of Dendritic Spines, Dendritic Shafts, and Axonal Boutons in Hippocampal Neuropil. Front Cell Neurosci 12:248 |
