Electronic Theses and Dissertations

Date of Award


Document Type


Degree Name

M.S. in Biological Science



First Advisor

Nicole M. Ashpole

Second Advisor

Jason A. Paris

Third Advisor

Gregg G. Roman

Relational Format



Modern medicine has consistently extended life expectancy over recent decades and centuries. Despite this, age-associated cognitive decline and risk of neurodegenerative disease grow in parallel with lifespan, meaning the capacity to live healthier has not mirrored that to live longer. Many studies in both human and rodents have shown the association between age-related cognitive impairment and reduction of insulin-like growth factor-1 (IGF-1) signaling. Additional research has indicated that dysregulated IGF-1 signaling, either systemic or local to the central nervous system (CNS) in cells like neurons and glia, leads to impaired spatial learning and memory in mice. Glia, or glial cells, like astrocytes and microglia are industrious in maintaining homeostasis, driving metabolic processes and providing neuroprotective support in the brain. Activation of glia characterized by functional, transcriptional, and morphological changes is strongly implicated in age-related neuropathology whether as an immunoreactive defense or a propellant of harmful stimuli. Expanding upon the autocrine/paracrine nature of IGF-1 in consideration of the protective roles glia play in preserving cerebral function, we specifically reduced IGF-1 production in astrocytes in vivo using a transgenic mouse model (aIGF1-KO) to assess the contribution that astrocytes have in maintaining the appropriate levels of IGF-1 within the brain to promote normal cognitive function and mediate lipopolysaccharide-induced (LPS) neuroinflammatory responses in regards to glial morphology and distribution. Our results show that reduction of astrocytic IGF-1 in female mice increases anxiety-like behavior and impairs spatial learning and memory. Additionally, female aIGF1-KO mice receiving LPS exhibited locomotor deficits, but extent of memory impairment and overall cognitive flexibility were unaltered. On the other hand, male aIGF1-KO mice exhibited improved spatial learning and memory, but astrocytic IGF-1 deficiency in males did not alter the effects of LPS on locomotor function, memory retrieval, or cognitive flexibility. Furthermore, hippocampal GFAP+ astrocytes in male aIGF-1 KO mice showed unaltered complexity but increased cell density, however this effect was abrogated with exposure to LPS.

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