Date of Degree

2-2014

Document Type

Dissertation

Degree Name

Ph.D.

Program

Psychology

Advisor

Susan D. Croll

Subject Categories

Medicine and Health Sciences | Neuroscience and Neurobiology

Keywords

Astrocytes, Behavioral Preservation, Epilepsy, Growth Factors, VEGF

Abstract

VEGF treatment during pilocarpine-induced status epilepticus (SE) causes enduring preservation of behavioral function in rats in the absence of enduring neuroprotection (Nicoletti et al., 2010). In addition, VEGF treatment reduces hyperexcitability in hippocampal slices without altering neuronal membrane properties (McCloskey et al, 2005). Combined, these data suggest the possibility that other cells or mechanisms could be involved in the beneficial effects of VEGF during SE. Our laboratory is interested in the potential contribution of astrocytes to these effects. Astrocytes are not only reported to contribute to epileptiform discharges in the hippocampus (Tian et al., 2005; Kang et al., 2005) but also to express VEGF receptors (Krum & Rosenstein, 2002). We previously reported that VEGF treatment significantly alters multiple astrocyte parameters such as cell soma size, branching complexity, branch volume, number of dendrites, nodes counts and highest order branching after SE. The current study investigated both astrocyte morphology and glutamate transporter expression one month after SE in animals treated with VEGF or inactivated VEGF during SE. Individual GFAP-immunostained astrocytes from both CA1 and the dentate gyrus hilus were traced using Neurolucida software (Microbrightfield Inc.), allowing morphological parameters to be analyzed via Branched Structure and Sholl analyses. In addition, Image J software was used to measure optical density in GLT1 (glial glutamate transporter 1)-immunostained sections. VEGF treatment during SE significantly prevented post-SE increases in number of branch intersections, process length, and node count. Furthermore, an analysis of the distance to the nearest neighboring astrocyte revealed that VEGF treatment significantly increased inter-astrocyte distance. GLT1 immunoreactivity in VEGF treated animals was decreased compared to seized controls. VEGF treatment did not significantly alter the shape of the astrocytes but rather the branching complexity and size. Because cell morphology impacts cell physiology, it is possible that VEGF's enduring effects on post-SE astrocyte morphology impacts the functioning of the post-seizure hippocampus.

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