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Open Access Highly Accessed Research article

Renal nerve ultrastructural alterations in short term and long term experimental diabetes

Karina Laurenti Sato13, Luciana Sayuri Sanada13, Renata da Silva Ferreira13, Maria Carolina del Bem de Barros Oliveti de Marco13, Jaci Airton Castania2, Helio Cesar Salgado2, Randy Alan Nessler3 and Valeria Paula Sassoli Fazan134*

Author Affiliations

1 Departments of Neurosciences and Behavioral Sciences, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil

2 Departments of Physiology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil

3 Central Microscopy Research Facility, The University of Iowa, Iowa City, IA, USA

4 Dept. of Surgery and Anatomy, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil

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BMC Neuroscience 2014, 15:5  doi:10.1186/1471-2202-15-5

Published: 5 January 2014

Abstract

Background

Despite the evidence that renal hemodynamics is impaired in experimental diabetes, associated with glomeruli structural alterations, renal nerves were not yet investigated in experimental models of diabetes and the contribution of nerve alterations to the diabetic nephropathy remains to be investigated. We aimed to determine if ultrastructural morphometric parameters of the renal nerves are affected by short term and/or long term experimental diabetes and if insulin treatment reverses these alterations. Left renal nerves were evaluated 15 days or 12 weeks (N = 10 in each group) after induction of diabetes, with a single injection of streptozotocin (STZ). Control rats (N = 10 in each group) were injected with vehicle (citrate buffer). Treated animals (N = 10 in each group) received a single subcutaneous injection of insulin on a daily basis. Arterial pressure, together with the renal nerves activity, was recorded 15 days (short-term) or 12 weeks (long-term) after STZ injection. After the recordings, the renal nerves were dissected, prepared for light and transmission electron microscopy, and fascicle and fibers morphometry were carried out with computer software.

Results

The major diabetic alteration on the renal nerves was a small myelinated fibers loss since their number was smaller on chronic diabetic animals, the average morphometric parameters of the myelinated fibers were larger on chronic diabetic animals and distribution histograms of fiber diameter was significantly shifted to the right on chronic diabetic animals. These alterations began early, after 15 days of diabetes induction, associated with a severe mitochondrial damage, and were not prevented by conventional insulin treatment.

Conclusions

The experimental diabetes, induced by a single intravenous injection of STZ, in adult male Wistar rats, caused small fiber loss in the renal nerves, probably due to the early mitochondrial damage. Conventional treatment with insulin was able to correct the weight gain and metabolic changes in diabetic animals, without, however, correcting and / or preventing damage to the thin fibers caused by STZ-induced diabetes. The kidney innervation is impaired in this diabetic model suggesting that alterations of the renal nerves may play a role in the development of the diabetic nephropathy.

Keywords:
Renal nerve; Ultrastructure; Unmyelinated fibers; Diabetic neuropathy