Honors Theses

Date of Award

Fall 5-8-2022

Document Type

Undergraduate Thesis

Department

Biology

First Advisor

Nicole Ashpole

Second Advisor

Jason Paris

Third Advisor

Dale Nagle

Relational Format

Dissertation/Thesis

Abstract

Chronic inflammation is a driver of numerous neurodegenerative diseases that reduce quality of life for affected individuals. Non-psychoactive cannabinoids have begun to gain more interest in the world of anti-inflammatory medicine for chronically ill patients. Along with these cannabinoids, insulin-like growth factor-1 has been examined for its association with downregulation of inflammation. Our research aimed to investigate how neuroglia are affected by treatment with cannabinoids or IGF-1 in the face of inflammation from HIV-1 protein, Tat, or lipopolysaccharide (LPS). Preliminary studies in our laboratory showed that neither cannabinoids or IGF-1 treatment altered astrocyte morphology or overall astrocyte viability under baseline conditions, indicating no overt consequences of IGF-1 or cannabinoid treatment. Therefore, we hypothesized that cannabinoids and IGF-1 treatment would counteract astrogliosis induced by the key inflammatory mediators- tat and LPS. Numerous cannabinoids were assessed, with cannabidiol (CBD) showing significant effects across numerous measures of cell morphology and viability in the presence of Tat. No differences were observed when IGF-1 was administered. We also investigated whether astrocyte-derived IGF-1 would alter the number and size of microglia (Iba1+ cells) present in a sample of hippocampus tissue following systemic inflammation with LPS. We predicted that mice with astrocytic-IGF-1 knockout would suffer

more heavily from the neuroinflammatory effects of LPS. Surprisingly, the effects were minimal and indicated sex- and region-dependence, despite systemic inflammation in both males and females. Additional work is on-going to assess astrocyte response, as well as to assess the effects of cannabinoids on microglial and astroglial activation in mice exposed to chronic inflammation. Together, we hoped to clarify the protective capabilities of IGF-1 and cannabinoids on astrocytic and microglial cells, both of which hold an important role in neurological conditions.

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