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

Abstract

BackgroundDespite 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.ResultsThe 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.ConclusionsThe 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.

Synaptic input changes to spinal cord motoneurons correlate with motor control impairments in a type 1 diabetes mellitus model

“…; Sato et al. ). Moreover, the nervous system is also affected leading to complications at the CNS (central nervous system) and PNS (peripheral nervous system) levels (Zochodne et al.…”

“…Diabetes mellitus (DM) is the most common metabolic disorder in humans (Beauquis et al 2008) involving a group of related diseases characterized by hyperglycemia as a result of insufficient insulin secretion, insulin resistance, or both (Gispen and Biessels 2000). The long-term complications of the disease affect the visual system, kidneys, heart, and blood vessels (Beauquis et al 2008;Oliveira et al 2013;Sato et al 2014). Moreover, the nervous system is also affected leading to complications at the CNS (central nervous system) and PNS (peripheral nervous system) levels (Zochodne et al 2008).…”

Assessment of Glomerular Filtration Rate Based on Alterations of Serum Brain-Derived Neurotrophic Factor in Type 2 Diabetic Subjects Treated with Amlodipine/Benazepril or Valsartan/Hydrochlorothiazide

“…Alterations in renal nerves have been observed in diabetic subjects, and this neural damage might result in dysfunctional regulation of renal blood flow [25, 26]. Sympathetic overactivation has been reported to be associated with diabetic nephropathy [26].…”

Acute Experimental Diabetes and Aortic Depressor Nerve Ultrastructural Morphometry: Effects of Insulin Treatment

“…For the ultrastructural studies, thin transverse sections were mounted on Formvar coated 2×1 slot grids, stained with lead citrate and uranyl acetate, and observed with a JEM-1230 transmission electron microscope (JEOL-USA, Inc., Peabody, MA, USA) equipped with a digital camera. Using the image analysis software, the total number of the unmyelinated fibers was counted, and their diameter measured as described [11,[19][20][21]. The density of the unmyelinated fiber was calculated and the ratio between unmyelinated/myelinated fibers was determined.…”

“…basement membrane as well as thickening of the perineural cell basement membrane [22][23][24][25]. Thickening of the Schwann cells basement membrane was less reported, either in humans [25] or in experimental diabetes [21]. The extracellular matrix in peripheral nerves gives mechanical support to the surrounding cells.…”