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Investigation of the anti-inflammatory effect of curcumin in a mouse model of chronic neuroinflammation – a route for a cure for Alzheimer’s disease?

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  • Full or part time
    Dr E Gyengesi
    Prof Gerald Muench
  • Application Deadline
    Applications accepted all year round
  • Competition Funded PhD Project (Students Worldwide)
    Competition Funded PhD Project (Students Worldwide)

Project Description

This project will investigate the effect of chronic glial activation on brain structure and function, and test the efficacy of two cytokine-suppressive anti-inflammatory drugs (CSAIDs) against chronic glial activation and the resulting neuronal damage. Activation of microglia and astroglia is a pathological process evident in many neurodegenerative diseases, including Alzheimer’s disease. The currently used anti-inflammatory drugs such as NSIADs and corticosteroids have shown limited effects in many neuroinflammatory diseases. Consequently, it has been suggested that drugs targeting neuroinflammation such as CSAIDs might yield disease-modifying treatments for these neurodegenerative disorders.

We will explore the GFAP-IL6 mouse, in which chronic neuroinflammation is induced by astroglia-specific production of interleukin 6 (IL6). We will use a variety of behavioural tests to monitor motor skills and cognitive functions in these mice up to 24 months of age. Furthermore, the anti-inflammatory effects of two CSAIDs (curcumin and apigenin) will be tested in this model, first in a dose-response study, and then in prevention and a treatment studies. In the diagnostic/imaging arm of our study, we will investigate whether chronic neuroinflammation can be detected in our mouse model using a PET tracer for the 18 kDa translocator protein (TSPO), a marker of activated microglia. This will allow us to follow the success of treatment of neuroinflammation by CSAID in the live mouse.

Methods: Techniques involved will be immunohistochemistry, stereology, 3D reconstruction using MBF Neurolucida/Stereoinvestigator and/or behavioural analysis. Previous experience with these techniques are an advantage.

Funding Notes

International scholarships available:
https://www.westernsydney.edu.au/graduate_research_school/grs/scholarships/main_round_scholarships

References

https://www.westernsydney.edu.au/medicine/som/hdr



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