Undergraduate Honors Theses

Thesis Defended

Spring 2019

Document Type

Thesis

Type of Thesis

Departmental Honors

Department

Psychology & Neuroscience

First Advisor

Dr. Linda Watkins

Abstract

Over the last century, members of post-industrial societies have experienced a significant depletion of gut microbiota in terms of parasitic “old friends”. Consequently, the ability of the remaining microbiota to modulate immune responses has been drastically limited. Reduced immunoregulation causes the immune system to be overactive due to an improper balance between T helper 1 (Th1) and T helper 2 (Th2) immunity. Th1 immunity is used to fight intracellular pathogens, and it is mediated by inflammatory effector T cells. Th2 immunity fights extracellular pathogens through a humoral response that upregulates antibody production. It has been demonstrated that intestinal helminth worms, such as Hymenolepis diminuta, are responsible for a shift away from Th1 cell immunity and towards Th2 cell immunity, which promotes an anti-inflammatory phenotype through suppression of inflammatory effector T cells. A helminth-induced anti-inflammatory shift could potentially be used to counteract inflammatory disorders such as chronic neuropathic pain. Neuropathic pain is responsible for an upregulation of pro-inflammatory cytokines and a shift toward Th1 immunity. This study explored the use of helminthic therapy as a treatment for neuropathic pain in the periphery and both neuropathic pain and cognitive dysfunction in the central nervous system through increased immune regulation.

We investigated the effects of H. diminuta on neuropathic pain development and cognition in male Sprague Dawley rats following chronic constriction injury of the sciatic nerve. Rats were colonized with Hymenolepid diminuta cystercercoids (HDCs; larval stage) prior to CCI surgeries. Von Frey testing measured levels of mechanical allodynia, Pavlovian fear conditioning measured declarative memory, and juvenile social exploration measured levels of anxiety. Inconsistent results from Von Frey and fear conditioning suggest that helminth worm therapy most likely does not improve mechanical allodynia or hippocampal-dependent learning and memory cognition. Neither CCI surgery nor helminth colonization impacted anxiety levels. Additionally, impacts of H. diminuta on molecular regulation of cytokine levels in the hippocampus were assessed using qRT-PCR. Hippocampus analysis demonstrated a shift toward an anti-inflammatory cytokine milieu following helminth treatment. These studies indicate that, although helminths did not consistently impact behavior following CCI surgeries, H. diminuta therapy is a promising treatment for neuroinflammation in the brain.

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