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  A neuroprotective role for Schwann cell glycogen in sciatic nerve diabetic neuropathy


   School of Life Sciences

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  Dr A Brown  Applications accepted all year round  Self-Funded PhD Students Only

About the Project

We have established that glycogen is present in sciatic nerves of mice, the first such description; we aim to determine the potential for glycogen as an endogenous neuroprotective agent that supports axons in peripheral nerves during diabetes. Experiments will be carried out on normal and diabetic mice. Electron microscopy will be used to localize the glycogen to particular cellular compartments and determine if glycogen distribution is altered in diabetes, which may result in altered axonal conductivity and vulnerability during periods of impaired neuronal blood flow in diabetics. Measuring the sensitivity of this glycogen depot to insulin and glucose will determine the capacity of this energy reserve to be regulated and see whether it is altered during diabetes. Parallel electrophysiological experiments and biochemical assays will determine the relationship between stimulus evoked compound action potentials, glycogen content and non-glucose energy substrates. Initial results suggest that glycogen selectively supports large fibres, but not the small fibres during glucose withdrawal, suggesting that the small axons are not protected by glycogen and that disruption of the relationship between glycogen and large axons may render the large fibres vulnerable to injury. Our research addresses this question.

The University of Nottingham is one of the world’s most respected research-intensive universities, ranked 8th in the UK for research power (REF 2014). Students studying in the School of Life Sciences will have the opportunity to thrive in a vibrant, multidisciplinary environment, with expert supervision from leaders in their field, state-of-the-art facilities and strong links with industry. Students are closely monitored in terms of their personal and professional progression throughout their study period and are assigned academic mentors in addition to their supervisory team. The School provides structured training as a fundamental part of postgraduate personal development and our training programme enables students to develop skills across the four domains of the Vitae Researcher Development Framework (RDF). During their studies, students will also have the opportunity to attend and present at conferences around the world. The School puts strong emphasis on the promotion of postgraduate research with a 2-day annual PhD research symposium attended by all students, plus academic staff and invited speakers.

Funding Notes

Home applicants should contact the supervisor to determine the current funding status for this project. EU applicants should visit the Graduate School webpages for information on specific EU scholarships http://www.nottingham.ac.uk/GraduateSchool/index.aspx. International applicants should visit our International Research Scholarships page for information regarding fees and funding at the University http://www.nottingham.ac.uk/studywithus/international-applicants/scholarships-fees-and-finance/index.aspx.

References

Allen LM, Anderson S, Wender R, Meakin PJ, Ransom BR, Ray DE & Brown AM.
(2006). Fructose supports energy metabolism of some, but not all, axons in adult
mouse optic nerve. Journal of Neurophysiology 95, 1917-1925.
Brown AM, Baltan Tekkök S & Ransom BR. (2003). Glycogen regulation and
functional role in mouse white matter. Journal of Physiology 549.2, 501-512.
Brown AM, Sickmann HM, Fosgerau K, Lund TM, Schousboe A, Waagepetersen HS
& Ransom BR. (2005). Astrocyte glycogen metabolism is required for neural activity
during aglycaemia or intense stimulation in mouse white matter. Journal of
Neuroscience Research 79, 74-80.
Brown AM, Wender R & Ransom BR. (2001). Metabolic substrates other than glucose
support axon function in central white matter. Journal of Neuroscience Research 66,
839-843.
Brown AM, Evans RD, Black J, and Ransom BR. Schwann cell glycogen selectively supports myelinated axon function. Ann Neurol 72: 406-418, 2012.
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and insulin resistance in NONcNZO10/LtJ males, a new mouse model of type 2
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Kalichman MW, Powell HC & Mizisin AP. (1998). Reactive, degenerative, and
proliferative Schwann cell responses in experimental galactose and human diabetic
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Pfeiffer-Guglielmi B, Francke M, Reichenbach A & Hamprecht B. (2007). Glycogen
phosphorylase isozymes and energy metabolism in the rat peripheral nervous
system--an immunocytochemical study. Brain Res 1136, 20-27.
Powell HC, Haas R, Hall CL, Wolff JA, Nyhan W & Brown BI. (1985). Peripheral nerve
in type III glycogenosis: selective involvement of unmyelinated fiber Schwann cells.
Muscle Nerve 8, 667-671.

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