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Investigating the effectiveness of low-intensity pulsed ultrasound (LIPUS) in reducing type 2 diabetes induced peripheral neuropathy and pain.

  • Full or part time
  • Application Deadline
    Applications accepted all year round
  • Self-Funded PhD Students Only
    Self-Funded PhD Students Only

Project Description

Diabetes is a serious health issue in developed and developing countries. About 415 million adults have diabetes, a number that is estimated to increase by 50% in 20 years. One of the most debilitating complications of diabetes is Diabetic Peripheral Neuropathy (DPN). DPN is characterised by a progressive distal to proximal degeneration of peripheral nerves which results in pain, loss of sensation and weakness. At least half of diabetics develop DPN. Neuropathy affecting small diameter fibers appear first leading to allodynia and hyperalgesia, then loss of sensation. It is not known whether this is due to changes in different populations of sensory neurons or sequential changes in the same neurons. It is also not known how much of the changes in sensory neurons are intrinsic or due to their interaction with glia cells (Schwan).

The first aim of this project it to address these questions. We aim to characterise the chronological development and nature of changes in the excitability of cultured sensory neurons in the type 2 diabetes db/db mouse model (one of the most widely used models of Type 2 Diabetes). The functional characterisation will be based on the excitability assay we recently developed for mouse cultured sensory neurons [2; 3] . This assay is simple to undertake but generates a wealth of data including baseline calcium signal, number of responding neurons, size of response, onset of response, size and pharmacological profile of responding neurons.

The second key component of the project will be to investigate whether neuron degeneration can be combated by low-intensity pulsed ultrasound (LIPUS), an emerging therapy. LIPUS has been found to promote regeneration of peripheral nerves subjected to physical injury by affecting both Schwann cells and neurons [1]. This second aim of the project is to investigate whether daily application of LIPUS can prevent the neuropathic degeneration of neurons in diabetic mice, by comparing the excitability of neurons dissected from treated and untreated mice. The project therefore advances our understanding of DPN and tests a clinical therapy.

Science Graduate School
As a PhD student in one of the science departments at the University of Sheffield, you’ll be part of the Science Graduate School. You’ll get access to training opportunities designed to support your career development by helping you gain professional skills that are essential in all areas of science. You’ll be able to learn how to recognise good research and research behaviour, improve your communication abilities and experience the breadth of technologies that are used in academia, industry and many related careers. Visit http://www.sheffield.ac.uk/sgs to learn more


Funding Notes

Entry requirements
First class or upper second 2(i) in a relevant subject. To formally apply for a PhD, you must complete the University's application form using the following link: View Website

*All applicants should ensure that both references are uploaded onto their application as a decision will be unable to be made without this information*.

References

References
[1] Jiang W, Wang Y, Tang J, Peng J, Wang Y, Guo Q, Guo Z, Li P, Xiao B, Zhang J. Low-intensity pulsed ultrasound treatment improved the rate of autograft peripheral nerve regeneration in rat. Sci Rep 2016;6:22773.
[2] Mohammed Z, Kaloyanova K, Nassar MA. An unbiased and efficient assessment of excitability of sensory neurons for analgesic drug discovery. Pain 2020.
[3] Mohammed ZA, Doran C, Grundy D, Nassar MA. Veratridine produces distinct calcium response profiles in mouse Dorsal Root Ganglia neurons. Sci Rep 2017;7:45221.

Related Subjects

How good is research at University of Sheffield in Biological Sciences?

FTE Category A staff submitted: 44.90

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