Milken Institute School of Public Health Poster Presentations (Marvin Center & Video)

Title

Intraviterious injection approaches to ablate optic nerve astrocytes

Document Type

Poster

Keywords

astrocytes, oligodendrocytes, multiple sclerosis, myelination

Publication Date

Spring 5-1-2019

Abstract

Astrocytes and oligodendrocytes are the major glial cells present in the central nervous system. While oligodendrocytes play a major role in myelin formation, astrocytes are involved in blood brain barrier formation, neuronal guidance, structural support, and glial scar formation. Astrocytes are also involved in various aspects of oligodendrocyte development and myelination. To study the effects of astrocytes on oligodendrocytes and myelination in the optic nerve, we have used intraviterious injection in transgenic mice (GFAP-iCP9) in which apoptosis in a subset of astrocytes was achieved by an inducible form of caspase 9 (iCP9) driven by a fragment of the glial fibrillary acidic protein (GFAP) promoter tagged by DsRed. Data indicate intraviterious injection as an effective method to abolish a subset of astrocytes in the optic nerve, which initiates microglial activation and myelin perturbation 2 days after injection. Furthermore, our studies reveal two populations (GFAP+/DsRed+ and GFAP+/DsRed-) of astrocytes that may be derived from different precursor populations suggesting functional heterogeneity among astrocytes. Future studies will aim at studying the response of oligodendrocytes and myelin at defined time points after astrocyte ablation and utilizing RNA-seq to evaluate the gene expression profiles of the two populations of astrocytes in the optic nerve.

Open Access

1

Comments

Presented at Research Days 2019.

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Intraviterious injection approaches to ablate optic nerve astrocytes

Astrocytes and oligodendrocytes are the major glial cells present in the central nervous system. While oligodendrocytes play a major role in myelin formation, astrocytes are involved in blood brain barrier formation, neuronal guidance, structural support, and glial scar formation. Astrocytes are also involved in various aspects of oligodendrocyte development and myelination. To study the effects of astrocytes on oligodendrocytes and myelination in the optic nerve, we have used intraviterious injection in transgenic mice (GFAP-iCP9) in which apoptosis in a subset of astrocytes was achieved by an inducible form of caspase 9 (iCP9) driven by a fragment of the glial fibrillary acidic protein (GFAP) promoter tagged by DsRed. Data indicate intraviterious injection as an effective method to abolish a subset of astrocytes in the optic nerve, which initiates microglial activation and myelin perturbation 2 days after injection. Furthermore, our studies reveal two populations (GFAP+/DsRed+ and GFAP+/DsRed-) of astrocytes that may be derived from different precursor populations suggesting functional heterogeneity among astrocytes. Future studies will aim at studying the response of oligodendrocytes and myelin at defined time points after astrocyte ablation and utilizing RNA-seq to evaluate the gene expression profiles of the two populations of astrocytes in the optic nerve.