Mutapi, Francisca

Picozzi, Kim

Cosgrove, Daniel

2023-01-31T17:10:06Z

2023-01-31T17:10:06Z

2019-06-29

Heligmosomoides polygyrus is a solely enteric helminth parasite that infects mice. It has recently been reported that infection of this parasite elicits a systemic increase in type-I interferon expression. This response is likely a result of the translocation of microbiota elements during the burrowing of the L3 larvae into the duodenal wall. This elevated level of interferon is potentially detrimental to the cognition of infected mice as interferon beta (Ifnb1) induces the production of CXCL10, which acts as a ligand for CXCR3 receptors. Sustained CXCR3 activation in the brain has previously been shown to inhibit neural plasticity, thus affecting mood, behaviour and cognition. Given that 880 million children worldwide are currently estimated to be infected with intestinal parasites, the potential for developmental morbidity is great. Using qPCR, transcripts of Ifnb1, CXCL10 and a plethora of related pathway factors were measured and analysed to determine expressional differences in 4 key brain regions of infected individuals. Alongside these inflammatory factors, qPCR analysis of immediate early genes (IEGs) was also performed to further explore the potential cognitive effects of H. polygyrus infection, on an expressional level. Given that these genes are associated with discovery and the learning of new surroundings, we hypothesise that there will be a decrease in expression in the infected mice. To determine the location of interferon expression in the brain, transgenic GFP interferon reporter mice were infected with H. polygyrus and subsequently examined using a fluorescent microscope, as well as being subjected to interferon beta antigen retrieval. No distinguishable difference was found between the naïve and infected sample brain tissues; however, the qPCR findings suggest that future work should include the analysis of other pathway factors that are expressed at a higher level. This project attempts to outline and further characterise the pathway leading to cognitive decline post parasitic infection.

https://hdl.handle.net/1842/39789

http://dx.doi.org/10.7488/era/3037

en

The University of Edinburgh

Helminth

H.polygyrus

Cognition

CXCL10

interferon

murine

Intestinal helminth infection and inflammatory responses in the murine brain

Thesis or Dissertation

Doctoral

MScR Infectious Diseases