Temporal dystrophic remodeling within the intrinsic cardiac nervous system of the streptozotocin-induced diabetic rat model

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dc.contributor.author Menard, Chantalle E
dc.contributor.author Durston, Melanie
dc.contributor.author Zherebitskaya, Elena
dc.contributor.author Smith, Darrell R
dc.contributor.author Freed, Darren
dc.contributor.author Glazner, Gordon W
dc.contributor.author Tian, Ganghong
dc.contributor.author Fernyhough, Paul
dc.contributor.author Arora, Rakesh C
dc.date.accessioned 2014-06-30T15:05:06Z
dc.date.available 2014-06-30T15:05:06Z
dc.date.issued 2014-06-04
dc.identifier.citation Acta Neuropathologica Communications. 2014 Jun 04;2(1):60
dc.identifier.uri http://hdl.handle.net/1993/23674
dc.description.abstract Abstract Introduction The pathogenesis of heart failure (HF) in diabetic individuals, called “diabetic cardiomyopathy”, is only partially understood. Alterations in the cardiac autonomic nervous system due to oxidative stress have been implicated. The intrinsic cardiac nervous system (ICNS) is an important regulatory pathway of cardiac autonomic function, however, little is known about the alterations that occur in the ICNS in diabetes. We sought to characterize morphologic changes and the role of oxidative stress within the ICNS of diabetic hearts. Cultured ICNS neuronal cells from the hearts of 3- and 6-month old type 1 diabetic streptozotocin (STZ)-induced diabetic Sprague-Dawley rats and age-matched controls were examined. Confocal microscopy analysis for protein gene product 9.5 (PGP 9.5) and amino acid adducts of (E)-4-hydroxy-2-nonenal (4-HNE) using immunofluorescence was undertaken. Cell morphology was then analyzed in a blinded fashion for features of neuronal dystrophy and the presence of 4-HNE adducts. Results At 3-months, diabetic ICNS neuronal cells exhibited 30% more neurite swellings per area (p = 0.01), and had a higher proportion with dystrophic appearance (88.1% vs. 50.5%; p = <0.0001), as compared to control neurons. At 6-months, diabetic ICNS neurons exhibited more features of dystrophy as compared to controls (74.3% vs. 62.2%; p = 0.0448), with 50% more neurite branching (p = 0.0015) and 50% less neurite outgrowth (p = <0.001). Analysis of 4-HNE adducts in ICNS neurons of 6-month diabetic rats demonstrated twice the amount of reactive oxygen species (ROS) as compared to controls (p = <0.001). Conclusion Neuronal dystrophy occurs in the ICNS neurons of STZ-induced diabetic rats, and accumulates temporally within the disease process. In addition, findings implicate an increase in ROS within the neuronal processes of ICNS neurons of diabetic rats suggesting an association between oxidative stress and the development of dystrophy in cardiac autonomic neurons.
dc.title Temporal dystrophic remodeling within the intrinsic cardiac nervous system of the streptozotocin-induced diabetic rat model
dc.type Journal Article
dc.language.rfc3066 en
dc.description.version Peer Reviewed
dc.rights.holder Chantalle E Menard et al.; licensee BioMed Central Ltd.
dc.date.updated 2014-06-30T15:05:06Z
dc.identifier.doi http://dx.doi.org/10.1186/2051-5960-2-60

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