Astrocytes are the largest population of glia cells in the central nervous system (CNS) that are vital for normal neuronal function. They closely interact with neurons as well as blood vessels. One of their major roles is to provide neurons with metabolic support through glial-vascular interactions allowing nutrient transport. They enwrap the vasculature with several unique anatomical structures that form a well-defined rosette-like architecture called end-feet processes. Although the role of astrocytes in the blood brain barrier (BBB) is poorly understood, they might be important for its maintenance due to the numerous receptors, transporters, and channels which mediate glial-endothelial communication and regulate the exchange of important factors through the glial-vascular interface. During both acute and chronic neurological disease, astrocytes become activated. They proliferate and display changes in morphology and gene expression, which can have an impact on neuronal function and might also affect the integrity of the BBB. On the other hand, there is evidence that the BBB may be affected during neurodegeneration and these changes may impact astrocyte's structure and function. Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the loss of cortical and spinal motor neurons, resulting in progressive paralysis and death. Supporting evidence has shown that the effects of ALS disease are not strictly limited to motor neurons. There are also prominent changes in morphology and function of spinal cord and motor cortex astroglia. In addition, during ALS there are vascular changes prior to motor neuron degeneration, but it is not known what roles the astrocytes play during these events. Although recent publications have documented changes in astrocytes beyond its glial fibrillary acidic protein (GFAP) upregulation, little effort has been dedicated to astrocytes surrounding blood vessels in regions of the motor cortex and spinal cord. In the current study, I propose to examine astroglial morphology surrounding blood vessels during acute and chronic cortical and spinal motor neuron degeneration using highly specific, non-injurious imaging tools including transgenic astroglia reporting mice. Results from this investigation will further our understanding of astroglial-vascular interactions, and the biology of astroglia/BBB in the setting of neurological disease.

Public Health Relevance

Astrocytes play a major role in providing neurons with metabolic support through their interaction with blood vessels. During the progression of a neurological disease, such as amyotrophic lateral sclerosis, there are prominent changes in astrocytes as well as blood vessels. This investigation will further our understanding of the structural changes and interactions between astrocytes and blood vessels in the context of motorneuron degeneration which are not yet fully understood.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Predoctoral Individual National Research Service Award (F31)
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Special Emphasis Panel (ZRG1-F01-F (20))
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Gubitz, Amelie
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Johns Hopkins University
Schools of Medicine
United States
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