Transport of myo-inositol into endoneurial preparations of sciatic nerve from normal and streptozotocin-diabetic rats.
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ABSTRACT:
SUBMITTER: Gillon KR
PROVIDER: S-EPMC1154289 | biostudies-other | 1983 Mar
REPOSITORIES: biostudies-other
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Project description:AimsTo investigate the candidate biomarkers and molecular mechanisms involved in the early phase of experimental diabetic peripheral neuropathy (DPN).MethodsDiabetes in Sprague-Dawley rats was induced with streptozotocin (STZ) treatment, followed with neurological tests and histological examinations to assess the neuropathic symptoms of DPN. Microarray was performed on the sciatic nerve tissues from control rats and DPN rats at then6th week after diabetes induction, and differentially expressed genes (DEGs) between them were identified and applied for further bioinformatic analyses.ResultsExperimental DPN rats were successfully constructed, presenting significantly decreased withdrawal threshold and motor nerve conduction velocity, and typical histological changes in the sciatic nerve. 597 DEGs (186 up- and 411 downregulated) were identified in DPN rats. DEGs from the 3 most highly connected clusters in the protein-protein interaction network were enriched for biological processes or pathways such as "cell division," "cell cycle," "protein phosphorylation," "chemokine signaling pathway," "neuropeptide signaling pathway," "response to drug," "cellular response to insulin stimulus," "PPAR signaling pathway," and "glycerophospholipid metabolism." Thirteen genes were identified as the hub DEGs in the PPI network. Eleven transcriptional factors (TFs) targeting 9 of the 13 hub DEGs were predicted.ConclusionsThe present study identified a pool of candidate biomarkers such as Cdk1, C3, Mapk12, Agt, Adipoq, Cxcl2, and Mmp9 and molecular mechanisms which may be involved in the early phase of experimental DPN. The findings provide clues for exploring new strategies for the early diagnosis and treatment of DPN.
| S-EPMC7256683 | biostudies-literature
Project description:Diabetic peripheral neuropathy (DPN) is a common microvascular complication of diabetes associated with high disability rate and low quality of life. Tang-Luo-Ning (TLN) is an effective traditional Chinese medicine for the treatment of DPN. To illustrate the underlying neural protection mechanisms of TLN, the effect of TLN on electrophysiology and sciatic nerve morphology was investigated in a model of streptozotocin-induced DPN, as well as the underlying mechanism. Sciatic motor nerve conduction velocity and digital sensory nerve conduction velocity were reduced in DPN and were significantly improved by TLN or α -lipoic acid at 10 and 20 weeks after streptozotocin injection. It was demonstrated that TLN intervention for 20 weeks significantly alleviated pathological injury as well as increased the phosphorylation of ErbB2, Erk, Bad (Ser112), and the mRNA expression of neuregulin 1 (Nrg1), GRB2-associated binding protein 1 (Gab1), and mammalian target of rapamycin (Mtor) in injured sciatic nerve. These novel therapeutic properties of TLN to promote Schwann cell survival may offer a promising alternative medicine for the patients to delay the progression of DPN. The underlying mechanism may be that TLN exerts neural protection effect after sciatic nerve injury through Nrg1/ErbB2→Erk/Bad Schwann cell survival signaling pathway.
| S-EPMC3830865 | biostudies-literature
Project description:Diabetes, with only mild ketosis, was induced in male rats by a single injection of streptozotocin. After 12 weeks the specific activities of enzymes concerned with the metabolism of inositol and of inositol lipids were measured in various tissues. Inositol 1-phosphate synthase (EC 5.5.1.4) was most active in testis and the activity was significantly less in diabetic rats than in controls on a similar diet. Inositol oxygenase (EC 1.13.99.1), which converts myo-inositol into glucuronic acid, was also less active in kidney from diabetic animals. CDP-diacylglycerol-inositol phosphatidyltransferase (EC 2.7.8.11) and phosphatidylinositol 4-phosphate kinase (EC 2.7.1.68) showed decreased specific activities in brain and sciatic nerve of diabetic rats. By contrast the diabetic state did not affect the specific activities of phosphatidylinositol kinase (EC 2.7.1.67) or phosphatidylinositol 4,5-bisphosphate phosphatase (EC 3.1.3.36) in these tissues. The results are discussed in relation to diabetic neuropathy.
| S-EPMC1186662 | biostudies-other
Project description:BackgroundOur study investigates the feasibility of using quantitative evaluation for nerve entrapment visualization by shear wave elastography (SWE) in diabetic rats.MethodsA total of 24 male Sprague-Dawley (SD) rats were included in this study. Before injection of streptozotocin (STZ), the experimental groups were assigned as the diabetic nerve compression (DNC) group (DNC, n=18) and the control group (CON, n=6). The DNC model was created by wrapping a silicone tube around the nerve, and then the DNC group was divided into the DNC 2-week (DNC2W, n=6), 4-week (DNC4W, n=6), and 8-week (DNC8W, n=6) groups according to the different duration time of sciatic nerve compression. The nerve stiffness was detected by SWE. Meanwhile, motor nerve conduction velocity (MNCV) was detected. These 2 indicators and histology of sciatic nerves were compared across the different groups.ResultsThe stiffness of the nerve depicted by SWE at the compression site increased markedly along with the duration time of compression (P<0.01). The MNCV decreased along with the duration time of nerve compression (P<0.05). The nerve stiffness depicted by SWE was negatively correlated with MNCV (r=-0.926; P<0.01). Myelinated fiber density significantly decreased as the duration time of nerve compression increased (P<0.01). Some differences were found between DNC4W and DNC8W groups, and CON and DNC2W groups (P<0.05) in average axon diameter, myelin sheath thickness, and g ratio.ConclusionsThe increased values of SWE, along with the increased duration of nerve compression, could reflect the severity of nerve entrapment in diabetic rats. Therefore, SWE may be used as a noninvasive and effective method to quantitatively evaluate the severity of diabetic nerve entrapment.
| S-EPMC7327375 | biostudies-literature
Project description:BACKGROUNDMyo-inositol (MI), successfully used in polycystic ovary syndrome (PCOS), was administered with ?-LA to exploit its action of favouring the passage of other molecules through biological barriers, and also considering its anti-inflammatory effect.METHODSPCOS patients, according to the Rotterdam ESHRE-ASRM criteria, with anovulation and infertility >?1 year, were included in this open and prospective study. The preliminary phase was aimed at determining a set of MI-resistant PCOS patients. This treatment involved 2 g MI, taken twice per day by oral route, for three months. The Homeostasis Model Assessment (HOMA) index and MI plasma levels were measured. In the main phase, previously selected MI-resistant patients received the same daily amount of MI plus 50 mg ?-LA twice a day, for a further three months. Ovulation was assessed using ultrasound examination on days 12, 14 and 20 of the cycle. The HOMA index, lipid, hormone and MI plasma levels were detected at baseline and at the end of this phase.RESULTSThirty-seven anovulatory PCOS subjects were included in the study. Following MI treatment, 23 of the 37 women (62%) ovulated, while 14 (38%) were resistant and did not ovulate. In the latter group, MI plasma levels did not increase. These MI-resistant patients underwent treatment in the main phase of the study, receiving MI and ?-LA. After this combined treatment, 12 (86%) of them ovulated. Their MI plasma levels were found to be significantly higher than at baseline; also, a hormone and lipid profile improvement was recorded.CONCLUSIONThe combination of MI with ?-LA allowed us to obtain significant progress in the treatment of PCOS MI-resistant patients. Therefore, this new formulation was able to re-establish ovulation, greatly increasing the chances of desired pregnancy.TRIAL REGISTRATIONClinical trial registration number: NCT03422289 ( ClinicalTrials.gov registry).
| S-EPMC5944130 | biostudies-literature
Project description:Spironolactone (SPR) has been shown to protect diabetic cardiomyopathy (DCM), but the specific mechanisms are not fully understood. Here, we determined the cardioprotective role of SPR in diabetic mice and further explored the potential mechanisms in both in vivo and in vitro models. Streptozotocin- (STZ-) induced diabetic rats were used as the in vivo model. After the onset of diabetes, rats were treated with either SPR (STZ?+?SPR) or saline (STZ?+?NS) for 12 weeks; nondiabetic rats were used as controls (NDCs). In vitro, H9C2 cells were exposed to aldosterone, with or without SPR. Cardiac structure was investigated with transmission electron microscopy and pathological examination; immunohistochemistry was performed to detect nitrotyrosine, collagen-1, TGF-?1, TNF-?, and F4/80 expression; and gene expression of markers for oxidative stress, inflammation, fibrosis, and energy metabolism was detected. Our results suggested that SPR attenuated mitochondrial morphological abnormalities and sarcoplasmic reticulum enlargement in diabetic rats. Compared to the STZ?+?NS group, cardiac oxidative stress, fibrosis, inflammation, and mitochondrial dysfunction were improved by SPR treatment. Our study showed that SPR had cardioprotective effects in diabetic rats by ameliorating mitochondrial dysfunction and reducing fibrosis, oxidative stress, and inflammation. This study, for the first time, indicates that SPR might be a potential treatment for DCM.
| S-EPMC6204188 | biostudies-literature
Project description:Diabetic nephropathy (DN) is a major complication of diabetes and is caused by an imbalance in the expression of certain genes that activate or inhibit vital cellular functions of kidney. Despite several recent advances, the pathogenesis of DN remains far from clear, suggesting the need to carry out studies identifying molecular aspects, such as gene expression, that could play a key role in the development of DN. There are several techniques to analyze transcriptome in living organisms. In this study, the suppression subtractive hybridization (SSH) method was used to generate up- and down-regulated subtracted cDNA libraries in the kidney of streptozotocin (STZ)-induced diabetic rats. Northern-blot analysis was used to confirm differential expression ratios from the obtained SSH clones to identify genes related to DN. 400 unique SSH clones were randomly chosen from the two subtraction libraries (200 of each) and verified as differentially expressed. According to blast screening and functional annotation, 20.2% and 20.9% of genes were related to metabolism proteins, 9% and 3.6% to transporters and channels, 16% and 6.3% to transcription factors, 19% and 17.2% to hypothetical proteins, and finally 24.1 and 17.2% to unknown genes, from the down- and up-regulated libraries, respectively. The down- and up-regulated cDNA libraries differentially expressed in the kidney of STZ diabetic rats have been successfully constructed and some identified genes could be highly important in DN.
| S-EPMC3257079 | biostudies-literature
Project description:BACKGROUND:Peripheral nerve stimulation is commonly used for nerve localization in regional anaesthesia, but recommended stimulation currents of 0.3-0.5 mA do not reliably produce motor activity in the absence of intraneural needle placement. As this may be particularly true in patients with diabetic neuropathy, we examined the stimulation threshold in patients with and without diabetes. METHODS:Preoperative evaluation included a neurological exam and electroneurography. During ultrasound-guided popliteal sciatic nerve block, we measured the current required to produce motor activity for the tibial and common peroneal nerve in diabetic and non-diabetic patients. Proximity to the nerve was evaluated post-hoc using ultrasound imaging. RESULTS:Average stimulation currents did not differ between diabetic (n=55) and non-diabetic patients (n=52). Although the planned number of patients was not reached, the power goal for the mean stimulation current was met. Subjects with diminished pressure perception showed increased thresholds for the common peroneal nerve (median 1.30 vs. 0.57 mA in subjects with normal perception, P=0.042), as did subjects with decreased pain sensation (1.60 vs. 0.50 mA in subjects with normal sensation, P=0.038). Slowed ulnar nerve conduction velocity predicted elevated mean stimulation current (r=-0.35, P=0.002). Finally, 15 diabetic patients required more than 0.5 mA to evoke a motor response, despite intraneural needle placement (n=4), or required currents ?2 mA despite needle-nerve contact, vs three such patients (1 intraneural, 2 with ?2 mA) among non-diabetic patients (P=0.003). CONCLUSIONS:These findings suggest that stimulation thresholds of 0.3-0.5 mA may not reliably determine close needle-nerve contact during popliteal sciatic nerve block, particularly in patients with diabetic neuropathy. CLINICAL TRIAL REGISTRATION:NCT01488474.
| S-EPMC4797685 | biostudies-literature
Project description:Diabetes mellitus (DM) is one of the most common chronic diseases around the world, and diabetic peripheral neuropathy (DPN) is one of the most common complications of DM. We used microarrays to identify the differentially expressed miRNAs in dorsal root ganglia (DRG) tissues from streptozotocin (STZ)-induced diabetic rats, taking normal SD rats as controls, and tried to find out the related genes which may be involved in the development of DPN.
2018-03-23 | GSE110231 | GEO
Project description:ObjectiveThe disordered growth of nerve stumps after amputation leading to the formation of neuromas is an important cause of postoperative pain in amputees. This severely affects the patients' quality of life. Regenerative peripheral nerve interfaces (RPNIs) are an emerging method for neuroma prevention, but its postoperative nerve growth and pathological changes are yet to be studied.MethodsThe rat sciatic nerve transection model was used to study the effectiveness of RPNI in this experiment. The RPNI (experimental) group (n = 11) underwent RPNI implantation after sciatic nerve transection, while the control group (n = 11) only underwent sciatic nerve transection. Autotomy behavior, ultrasonography, and histopathology were observed for 2 months postoperatively.ResultsCompared to the control group, the incidence and size of the neuromas formed and the incidence and extent of autotomy were significantly reduced in the RPNI group. The axon density in the stump and degree of stump fibrosis were also significantly reduced in the RPNI group.ConclusionRPNI effectively prevented the formation of neuromas.
| S-EPMC9301297 | biostudies-literature