Effect of the host gut microbiota on prion-induced neurodegeneration

Research output: Contribution to conferencePosterpeer-review

Abstract

Aims:
Neuropathological damage induced by prions within the CNS is a characteristic hallmark of prion diseases. Along with prion deposition and neuronal loss, striking changes in glial activation occur. Studying these changes within scrapie-infected mouse models reveals a tractable model to investigate the mechanisms of neurodegeneration. Recently there have been numerous reports that gut microbiota influence neurodegeneration via modulation of the CNS microglial population. Indeed studies in naive mice have suggested that lack of gut microbiota results in a reduction of microglial activation state and subsequent severity of CNS innate immune responses when subjected to stimulation by lipopolysaccharide (LPS). We therefore determined whether the host commensal microbiota may influence CNS prion disease pathogenesis and susceptibility.

Methods:
Germ-free mice were used to investigate the influence of the host microbiota on CNS prion disease pathogenesis and susceptibility. Germ-free mice and conventional mice (control) were injected with either the 22A and 22C mouse-passaged scrapie strains by the intracerebral or intraperitoneal routes. Following exposure, survival times were recorded and brains collected at the terminal stage of disease for histopathology. Brains from mice from each group were analysed by standard histopathological and immunohistochemistry, supplemented with image and morphometric analysis techniques.

Results:
Our data show that the host commensal microbiota did not influence prion disease duration or susceptibility, as survival times and disease incidences were identical in germ-free and conventional mice when infected by the same strain of agent via the same route. We observed previously characterised differences which occur in the severity and targeting of neuropathology within given brain regions based upon the strain of agent and route of infection. Germ-free mice have been shown to have altered microglial morphology in the naïve state when compared to those from conventional mice. However, our data show that at the terminal stage of prion disease, the neuropathological changes and microglial morphology were indistinguishable in brains from germ-free and conventional mice.

Conclusions:
Our data show that the presence or absence of the host commensal microbiota does not significantly influence the development of microglial activation or neuropathology within the CNS during prion disease.
Original languageEnglish
Publication statusPublished - 25 May 2017
EventPrion 2017 - Edinburgh, United Kingdom
Duration: 23 May 201726 May 2017

Conference

ConferencePrion 2017
Country/TerritoryUnited Kingdom
CityEdinburgh
Period23/05/1726/05/17

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  • Prion 2017

    Barry Bradford (Participant)

    23 May 201726 May 2017

    Activity: Participating in or organising an event typesParticipation in conference

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