Graduation Year

2020

Document Type

Thesis

Degree

M.S.

Degree Name

Master of Science (M.S.)

Degree Granting Department

Medical Sciences

Major Professor

Subhra Mohapatra, Ph. D.

Co-Major Professor

Daniel J Denmark, Ph. D.

Committee Member

Shyam S. Mohapatra, Ph. D.

Keywords

Nano-Particles, Thyroxin, LPS, GFAP, liposome-T4

Abstract

Astrocytes are the specialized cells in the central nervous system (CNS). They play an important role in neuronal homeostasis. When activated, astrocytes may cause neuronal inflammation and degeneration. Thyroid hormones are important in maintaining neuronal development and homeostasis. Astrocytes play a pivotal role in this process. However, the role of levothyroxine (T4) in neuroinflammation is not clear. It is hypothesized that thyroid hormone treatment will reduce the inflammatory activation in astrocytes. Available oral T4 supplementations allow accumulation of T4 in the body and cause toxicity and side effects. It is hypothesized that the encapsulation of T4 in liposomes would reduce toxicity and possibly help in brain targeted delivery. Astrocytes were activated in vitro by bacterial lipopolysaccharide (LPS) treatment for 24 hours with or without T4. We observed that LPS treatment increased glial fibrillary acidic protein (GFAP) expression in the astrocytes and changed the morphology of the cells indicating their activation. Treatment with T4 hormone simultaneously or prophylactically significantly reduced the GFAP expression and changed the morphology of the cells similar to nonactivated ones. These observations indicate that the thyroid hormone has an anti-inflammatory effect on LPS- induced astrocytes activation. Moreover, a liposomal T4 formulation was synthesized and characterized. Preliminary studies suggest that liposomal T4 was safe and taken-up by astrocytes and reduced LPS-induced astrocyte activation. More studies are required to confirm these observations.

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