Date of Award

12-1-2018

Language

English

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

College/School/Department

Department of Biomedical Sciences

Content Description

1 online resource (xv, 284 pages) : illustrations.

Dissertation/Thesis Chair

Sally Temple

Committee Members

Valerie Bolivar, Bruce Herron, Timothy Blenkinsop, Douglas Conklin

Keywords

Alzheimer's Disease, Cortex, Meninges, Organoid, Patterned, Regional, Central nervous system, Brain, Aging

Subject Categories

Neuroscience and Neurobiology

Abstract

The meninges comprise three heterogeneous connective tissue coverings, referred to as the dura, arachnoid, and pia mater, which completely envelop the brain and spinal cord. Given the meninges’ vast coverage over the entire CNS and its unique development, I hypothesized that regional leptomeninges (arachnoid and pia mater layers combined) provide specialized support to different brain areas. During development, anterior meninges, overlying the frontal cortex, derive from neural crest cells that are ectodermal in origin. Posterior meninges, overlying the midbrain to the spinal cord, derive from a mesodermal lineage. This difference in lineage and location suggests potential functional differences between the two regions. Work from this thesis compared the cellular, molecular, and functional support of regional leptomeninges to adjacent brain areas. To test this hypothesis, we identified adult regional leptomeninges as anterior leptomeninges (Am), overlying the temporal and dorsal parietal-temporal lobes, and posterior leptomeninges (Pm), overlying the occipital lobe adjacent to the midbrain and entorhinal cortex. We then compared Am and Pm using single-cell RNA sequencing, cytokine array, and in vitro culturing methods to determine the functional role of regional meninges on cortical cells.

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