, Volume 45, Issue 4, pp 560–570

Diabetes-induced alterations in calcium homeostasis in sensory neurones of streptozotocin-diabetic rats are restricted to lumbar ganglia and are prevented by neurotrophin-3


  • T.-J. Huang
    • School of Biological Sciences, University of Manchester, Manchester, UK
  • N. M. Sayers
    • School of Biological Sciences, University of Manchester, Manchester, UK
  • P. Fernyhough
    • School of Biological Sciences, University of Manchester, Manchester, UK
  • A. Verkhratsky
    • School of Biological Sciences, University of Manchester, Manchester, UK

DOI: 10.1007/s00125-002-0785-x

Cite this article as:
Huang, T., Sayers, N., Fernyhough, P. et al. Diabetologia (2002) 45: 560. doi:10.1007/s00125-002-0785-x


Aims/hypothesis. In diabetic sensory polyneuropathy the earliest and most severe pathophysiology occurs in neurones with the longest axons. The aim of this study was to characterise a diabetes-induced neurodegenerative marker that was selective for sensory neurones with the longest axons. We studied alterations in calcium homeostasis since this occurs in other neurodegenerative diseases. Methods. Sensory neurones were cultured from control and streptozotocin-diabetic rats, treated with or without human recombinant neurotrophin-3 (hrNT-3), and neurones from L4-L6 dorsal root ganglia (DRG) which exhibit the longest axons in vivo were compared with those from C5-L3 DRG. Fluorescent video-imaging was used to measure cytoplasmic calcium dynamics. Results. Streptozotocin diabetes of 8 to 14 weeks, induced an increase in resting internal Ca2+ concentration ([Ca2+]i), from 67 ± 7 nmol/l in small neurones and 79 ± 9 nmol/l in big neurones obtained from control animals to 214 ± 19 nmol/l in small neurones and 273 ± 30 nmol/l in big neurones after 14 weeks of diabetes (p < 0.05) in L4-L6 DRG cultures. Neurones from C5-L3 ganglia and non-neuronal cells were not affected. Treatment of 14-week streptozotocin-diabetic rats with subcutaneous injection of 5 mg/kg NT-3 normalised the increase in resting [Ca2+]i. The amplitudes induced by depolarisation, caffeine and ATP [Ca2+]i responses were reduced in small ( < 30μm diameter) but not big ( > 35μm diameter) neurones of L4-L6 DRG from streptozotocin-diabetic animals; the C5-L3 DRG were not similarly affected and the changes in the L4-L6 DRG were corrected by NT-3 treatment. Conclusions/interpretation. Altered calcium homeostasis could be an early molecular marker linked to the onset of diabetic sensory neuropathy. This neurodegenerative index can be corrected by NT-3 therapy and should encourage further work aimed at understanding the mechanistic basis of these observations. [Diabetologia (2002) 45: ▪–▪]

Keywords Diabetic neuropathyneurotrophinneurotrophin-3dorsal root gangliacalcium imagingsensory neuronepurinoreceptorcaffeine.
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© Springer-Verlag 2002