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Dr Jill Lincoln

Dr Jill Lincoln is a Senior Lecturer in Autonomic Neuroscience Her postdoctoral research has included studies of the nervous system in health and disease specialising in autonomic neuropathy in diabetes and the mechanisms underlying its development. This has resulted in the publication of over 60 articles subjected to peer review and she has also been a co-author of 10 book chapters and a book. j.lincoln@ucl.ac.uk Telephone: +44 (0) 20 7679 0479 (Int: 30479)

Damage to the nervous system, including autonomic nerves supplying the internal organs and blood vessels, occurs as a complication of diabetes mellitus. Such damage results in symptoms such as postural hypotension, disordered gut motility and impotence in diabetic patients and its presence is significantly correlated with decreased life expectancy. Using an animal model, we have demonstrated changes in autonomic nerves in the cardiovascular, gastrointestinal and urogenital systems. However, it is clear that not all autonomic nerves are affected in the same way in diabetes. Some nerves undergo degeneration, some have reduced levels of neurotransmitters and some appear to be largely unaffected. In order to find an explanation for this we are investigating possible mechanisms involved in causing nerve damage.

One factor of particular interest is oxidative stress induced by high levels of glucose in diabetes. Oxidative stress is a condition where there is an increase within cells of reactive molecules containing oxygen. These can then react with components of cells, including nerves, and cause damage. Nerves do have defence mechanisms against oxidative stress but they do not necessarily work to the same extent in different populations. Therefore, it is possible that autonomic nerves with a greater level of defence against oxidative stress may be able to resist the effects of diabetes while others with low levels of defence will be particularly susceptible to degenerative changes.

We are investigating the presence of oxidative stress and the status of defence mechanisms in a variety of autonomic nerves supplying the cardiovascular, gastrointestinal and urogenital systems that have been identified according to their neurotransmitter content. We are also looking at the changes that occur in diabetes and investigating the potential of various agents that can act against oxidative stress to prevent or even reverse autonomic nerve damage once it has occurred. In order to investigate the mechanisms involved in more detail we are currently developing in vitro models in which isolated sympathetic and myenteric neurons exposed to stimuli that mimic the diabetic environment replicate the changes that occur in vivo.

Support for this research has included funding from the Juvenile Diabetes Research Foundation International and the National Institutes of Health (USA).

Collaboration
Diminished sensation in the extremities due to neuropathy in diabetes can lead to the development of foot ulcers. Diabetes also impairs wound healing leading to the presence of chronic wounds prone to infection. This condition is the major cause of non-traumatic amputation in humans. Dr. David Becker is researching into the role of connexin proteins in gap junctions in the wound healing process. In collaboration we are investigating how diabetes affects the expression of specific connexins in intact skin and how it affects the dynamic changes in connexin expression that occur during the wound healing process. The aim of the research is also to examine whether manipulation of connexin expression can be used to improve wound healing in diabetes.

Profile
1970 BSc, University of Manchester
1973 PhD, University of Manchester
1977 Postdoctoral Research Assistant, Dept. Neuropathology, University of Manchester
1980 Postdoctoral Research Associate, Department of Anatomy and Developmental Biology, UCL
1988 Senior Research Fellow, Department of Anatomy and Developmental Biology, UCL
2002 Senior Lecturer, UCL

Selected Publications

Recent Peer-Reviewed Articles:

• Shotton, H.R., Clarke, S. & Lincoln, J. (2003) The effectiveness of treatments of diabetic autonomic neuropathy is not the same in autonomic nerves supplying different organs. Diabetes, 52: 157-164.
• Coutinho-Silva, R., Parsons, M., Robson, T., Lincoln, J. & Burnstock, G. (2003) P2X and P2Y purinoceptor expression in pancreas from streptozotocin-diabetic rats. Molecular & Cellular Endocrinology, 204: 141-154.
• Shotton, H.R., Broadbent, S. & Lincoln, J. (2004) Prevention and partial reversal of diabetes-induced changes in enteric nerves of the rat ileum by combined treatment with ?-lipoic acid and evening primrose oil. Autonomic Neuroscience: Basic and Clinical, 111: 57-65.
• Semra, Y.K., Smith, N.C.E. & Lincoln, J. (2004) Comparative effects of high glucose on different adult sympathetic neurons in culture. NeuroReport, 15: 2321-2325.
• Shotton, H.R. & Lincoln, J. (2006) Diabetes only affects nitric oxide synthase-containing myenteric neurons that do not contain haem oxygenase-2. Brain Research, 1068: 248-256.
• Semra, Y.K., Wang, M., Peat, N.J., Smith, N.C.E., Shotton, H.R. & Lincoln, J. (2006) Selective susceptibility of different subpopulations of sympathetic neurons to diabetic neuropathy in vivo is reflected by increased vulnerability to oxidative stress in vitro. Neuroscience Letters 407: 199-204.
• Shotton, H.R., Adams, A. & Lincoln, J. (2007) Effect of aminoguanidine treatment on diabetes-induced changes in the myenteric plexus of the rat ileum. Autonomic Neuroscience: Basic and Clinical, 132: 16-26.
• Wang C.M., Lincoln J., Cook J.E. & Becker D.L. (2007) Abnormal connexin expression underlies delayed wound healing in diabetic skin. Diabetes 56: 2809-2817.

Book:
Lincoln, J., Hoyle, C.H.V. & Burnstock, G. (1997) Nitric Oxide in Health and Disease. Cambridge University Press, Cambridge.

Chapters:
Milner, P., Lincoln, J. & Burnstock, G. (1999) The neurochemical organization of the autonomic nervous system, In: Handbook of Clinical Neurology Vol 74 (30) The Autonomic Nervous System, Part I – Normal Functions, Ed. Appenzeller, O., Elsevier Science, Amsterdam. pp. 87-134.
Lincoln, J. (2004) Nitrergic Neurotransmission, In: Primer on the Autonomic Nervous System, Ed. Robertson, D. Elsevier Science, San Diego, pp.90-92.
Lincoln, J. (2008) Free Radicals in Autonomic Function, In: New Encyclopedia of Neuroscience, Ed. Squire, LR. Elsevier, Oxford, In Press.