Nerve compression induces activating transcription factor 3 in neurons and Schwann cells in diabetic rats.
ABSTRACT Expression of transcription factor ATF3 in sensory neurons in dorsal root ganglion and in Schwann cells in sciatic nerve of diabetic (BB and Goto-Kakizaki rats; experimental models of types 1 and 2 diabetes, respectively) and healthy rats were examined by immunocytochemistry after nerve compression (silicone tube) for 3, 6 or 14 days. ATF3-stained sensory neurons in dorsal root ganglia and Schwann cells at compression site were more frequent in diabetic BB rats. Decompression of nerves in Goto-Kakizaki rats did not reduce number of ATF3-stained cells. Diabetes (BB; i.e. type 1) confers on the peripheral nerve an increased susceptibility to nerve compression indicated by an increased expression of stained ATF3 neurons and Schwann cells.
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ABSTRACT: Background In view of the global increase in diabetes, and the fact that recent findings indicate that diabetic neuropathy is more frequently seen in males, it is crucial to evaluate any gender differences in nerve regeneration in diabetes. Our aim was to evaluate in short-term experiments gender dissimilarities in axonal outgrowth in healthy and in genetically developed type 2 diabetic Goto-Kakizaki (GK) rats, and also to investigate the connection between activated (i.e. ATF-3, Activating Transcription Factor 3) and apoptotic (cleaved caspase 3) Schwann cells after sciatic nerve injury and repair. Female and male diabetic GK rats, spontaneously developing type 2 diabetes, were compared with corresponding healthy Wistar rats. The sciatic nerve was transected and instantly repaired. After six days the nerve was harvested to measure axonal outgrowth (i.e. neurofilament staining), and to quantify the number of ATF-3 (i.e. activated) and cleaved caspase 3 (i.e. apoptotic) stained Schwann cells using immunohistochemistry. Results Axonal outgrowth was generally longer in male than in female rats and also longer in healthy than in diabetic rats. Differences were observed in the number of activated Schwann cells both in the distal nerve segment and close to the lesion site. In particular the female diabetic rats had a lower number. There were no gender differences in number of cleaved caspase 3 stained Schwann cells, but rats with diabetes exhibited more (such cleaved caspase 3 stained Schwann) cells both at the lesion site and in the distal part of the sciatic nerve. Axonal outgrowth correlated with the number of ATF3 stained Schwann cells, but not with blood glucose levels or the cleaved caspase 3 stained Schwann cells. However, the number of cleaved caspase 3 stained Schwann cells correlated with the blood glucose level. Conclusions We conclude that there are gender differences in nerve regeneration in healthy rats and in type 2 diabetic GK rats.BMC Neuroscience 09/2014; 15(1):107. DOI:10.1186/1471-2202-15-107 · 2.85 Impact Factor
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ABSTRACT: Spinal sensory neurons innervating visceral and mucocutaneous tissues have unique microanatomical distribution, peripheral modality, and physiological, pharmacological and biophysical characteristics compared to those neurons that innervate muscle and cutaneous tissues. In previous patch clamp electrophysiological studies, we have demonstrated that small- and medium-diameter dorsal root ganglion (DRG) neurons can be subclassified based upon their patterns of voltage-activated currents (VAC). These VAC-based sub-classes were highly consistent in their action potential characteristics, responses to algesic compounds, immunocytochemical expression patterns, and responses to thermal stimuli. For this study, we examined the VAC of neurons retrogradely-traced from the distal colon and the glans penis / distal urethra in the adult male rat. The afferent population from the distal colon contained at least two previously characterized cell types observed in somatic tissues (Types 5 and 8), as well as four novel cell types (Types 15, 16, 17 and 18). In the glans penis / distal urethra, two previously described cell types (Types 6 and 8), and three novel cell type (Types 7, 14 and 15) were identified. Other characteristics, including action potential profiles, responses to algesic compounds (acetylcholine, capsaicin, ATP and pH 5.0 solution), and neurochemistry (expression of substance P, CGRP, neurofilament, TRPV1, TRPV2, and IB4-binding) were consistent for each VAC-defined subgroup. By identifying distinct DRG cell types that innervate the distal colon and glans penis / distal urethra, future in vitro studies related to the gastrointestinal and urogenital sensory function in normal, as well as abnormal/pathological conditions may be benefitted.Journal of Neurophysiology 05/2014; 112(6). DOI:10.1152/jn.00560.2013 · 3.04 Impact Factor
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ABSTRACT: Prolonged exposure to hand-held vibrating tools may cause a hand-arm vibration syndrome (HAVS), sometimes with individual susceptibility. The neurological symptoms seen in HAVS are similar to symptoms seen in patients with carpal tunnel syndrome (CTS) and there is a strong relationship between CTS and the use of vibrating tools. Vibration exposure to the hand is known to induce demyelination of nerve fibres and to reduce the density of myelinated nerve fibres in the nerve trunks. In view of current knowledge regarding the clinical effects of low nerve-fibre density in patients with neuropathies of varying aetiologies, such as diabetes, and that such a low density may lead to nerve entrapment symptoms, a reduction in myelinated nerve fibres may be a key factor behind the symptoms also seen in patients with HAVS and CTS. Furthermore, a reduced nerve-fibre density may result in a changed afferent signal pattern, resulting in turn in alterations in the brain, further prompting the symptoms seen in patients with HAVS and CTS. We conclude that a low nerve-fibre density lead to symptoms associated with nerve entrapment, such as CTS, in some patients with HAVS.Journal of Occupational Medicine and Toxicology 03/2014; 9(1):7. DOI:10.1186/1745-6673-9-7 · 1.23 Impact Factor