Phosphorylation and Fucosylation of Myelin Protein In Vitro by Sciatic Nerve from Developing Rats

Abstract: Proteins of the paniculate fraction of sciatic nerve of rats ranging from 1 to 55 days of age were analyzed by polyacrylamide gel electrophoresis. The major myelin protein, P₀, could not be detected at 1 day of age, but by 10 days it comprised from 15 to 20% of the particulate protein, the same proportion as in adult rats. Growth of nerve continued throughout the period studied. Rat sciatic nerves were incubated with [³²P]orthophosphate or [³H]fucose. Particulate matter proteins from sciatic nerve (and in certain cases proteins of myelin purified from sciatic nerve) were separated by polyacrylamide disc gel electrophoresis and the distribution of protein and of radioactivity along the gels was determined. [³²P]Phosphate appeared to label all myelin proteins. Labeling with fucose was more specific; myelin basic proteins were not fucosylated. A developmental study showed that sciatic nerves from 2-day-old rats could incorporate radioactive fucose and [³²P]-phosphate into several proteins at the P₀ region of polyacrylamide gels. Specific radioactivity of [³H]fucose in P₀ protein was highest in preparations from 5-day-old rats and declined by 80% over the next 5 days as it was diluted by accumulating myelin. The specific radioactivity of incorporated [³²P] phosphate was high at the early age points and declined as a result of the accumulation of compact myelin. The results indicate an association of fucosylation and/or phosphorylation with some step in the formation of myelin.     

Phorbol Ester-Mediated Stimulation of Phospholipase D Activity in Sciatic Nerve from Normal and Diabetic Rats

Evidence for the presence of phospholipase D activity in sciatic nerve was obtained by incubation of 32P-prelabeled nerve segments in the presence of ethanol and measurement of [32P]phosphatidylethanol (PEth) formation expressed as a fraction of total phospholipid radioactivity. PEth synthesis was enhanced with increasing concentrations of ethanol (100 mM-2 M). 4-beta-Phorbol dibutyrate (100 nM-1 microM) stimulated PEth formation up to twofold in a time- and dose-dependent manner. The stimulatory effect evoked by 100 nM phorbol ester was completely abolished by Ro 31-8220 (compound 3), a selective protein kinase C inhibitor. Efforts to identify the phospholipid precursor of PEth were unsuccessful, suggesting this product arises from a small discrete precursor pool. On subcellular fractionation of nerve, the ratio of basal and 4-beta-phorbol dibutyrate-stimulated phospholipase D activity recovered in a myelin-enriched fraction, compared with a nonmyelin fraction, was 0.5 when results are expressed as a percentage of total phospholipid radioactivity. This ratio rises to 1.2 if the results are calculated assuming only phosphatidylcholine and phosphatidylethanolamine are potential precursors. The results suggest that myelin is a major locus of phospholipase D activity. Nerve from streptozotocin-induced diabetic and control animals displayed the same basal phospholipase D activity, but the enzyme in diabetic nerve was stimulated to a greater extent by a suboptimal concentration of 4-beta-phorbol dibutyrate. These results support the conclusion that protein kinase C modulates phospholipase D activity in nerve and suggest that in diabetic nerve the enzyme activation mechanism may possess increased sensitivity.     

Alterations in mRNA Expression of Myelin Proteins in the Sciatic Nerves and Brains of Streptozotocin-induced Diabetic Rats

Diabetic neuropathy is the most common complication of diabetes. We examined the levels and the mRNA expression of myelin proteins in the sciatic nerves and the brains of streptozotocin-induced diabetic rats. The diabetic rats exhibited a decrease in body weight, elevation of the blood glucose level and a decrease in motor nerve conduction velocity at 2 weeks after streptozotocin injection. In the sciatic nerves of diabetic rats, the level of P0 protein and its mRNA expression were markedly reduced at 20 weeks after the injection. In the brains, the levels of proteolipid protein and myelin-associated glycoprotein and their mRNA expression were selectively decreased at 20 weeks after the injection. This affected expression of myelin proteins was found even when no histological abnormalities were detectable. Considering the functional significance of myelin proteins, this impairment of protein expression is possibly involved in the pathogenesis of diabetic neuropathy, including that in brain disorders.     

Protein and Glycoprotein Composition of Myelin Subfractions from the Developing Rat Optic Nerve and Tract

Abstract: The rat optic nerve and tract (representing a relatively homogeneous part of the CNS) were utilised for a detailed examination of the protein and glycoprotein composition of developing myelin membranes. Animals aged from 5 days through to adulthood were used. Myelin fractions could first be isolated from the nerve 8 days after birth and the yield increased until 60 days of age, before declining slightly to the adult level; a similar (but possibly slightly delayed) pattern was apparent for the optic tract. The homogeneity of optic nerve myelin (compared with that from brain and spinal cord) was demonstrated by zonal centrifugation on continuous sucrose-density gradients; myelin from both 20-day and adult animals exhibited narrow, Gaussian-like distributions, with 19–22% of the total myelin at the population modes. During development, the myelin density profile was shifted to a denser region of the sucrose gradients. Micro-polyacrylamide gel electrophoretic analyses of "light" and "heavy" myelin subfractions from both optic nerve and tract indicated that the gross developmental changes in protein composition were similar to those previously described for myelin prepared from larger CNS areas, particularly the forebrain. The glycoprotein components of the myelin fractions were stained directly on micro-gels using fluorescein isothiocyanate-labelled concanavalin A. The relative proportion of the major high-molecular-weight glycoprotein decreased rapidly during the early phases of myelination. A number of lower-molecular-weight glycoproteins were also apparent; the proportions of these varied during development and in light and heavy myelin subfractions, but definitive data are not available to determine whether they are components of the myelin sheath or of contaminating membranes.     

The PO Protein of Chick Sciatic Nerve Myelin: Purification and Partial Characterization

Abstract: The PO protein of the myelin of chick sciatic nerve was isolated and purified by propanoic acid extraction of peripheral nervous system (PNS) myelin, delipidation, Sepharose CL-6B chromatography in the presence of sodium dodecyl sulfate (SDS), and preparative SDS-polyacrylamide gel electro-phoresis (PAGE). Approximately 15% of the PO protein in the sciatic nerve myelin was recovered in a homogeneous state. The purified protein monomer has an apparent molecular weight of 32.1K as determined by gel electrophoresis. The PO protein undergoes extensive aggregation during exhaustive dialysis and freeze-drying and yields stable dimers, trimers, and tetramers. The aggregation of the PO protein after freeze-drying is independent of the presence of a reducing agent (2-mercaptoethanol) in the solubilizing medium. The PO protein is a glycoprotein. The amino acid composition of the chick PO protein indicates a definite species difference when compared with mammalian PO proteins although the NH₂-terminal isoleucine residue seems to have been retained during evolution.     

Identification of G Protein Subtypes in Peripheral Nerve and Cultured Schwann Cells

In this study, we investigated the expression of various G proteins in whole sciatic nerves, in myelin and nonmyelin fractions from these nerves, and in membranes of immortalized Schwann cells. In myelin, nonmyelin, and Schwann cell membranes we detected two 39-40-kDa pertussis toxin substrates that were resolved on separation on urea-gradient gels. Two cholera toxin substrates with apparent molecular masses of 42 and 47 kDa were present in nerve and brain myelin and in Schwann cell membranes. In these membranes, a third 45-kDa cholera toxin substrate, which displayed the highest labeling, was also present. Immunoblotting with specific antisera allowed the identification of G(o) alpha, Gi1 alpha, Gi2 alpha, Gi3 alpha, Gq/G11 alpha, and the two isoforms of Gs alpha in nerve homogenates, nerve, and brain myelin fractions. In Schwann cell membranes we identified G(o) alpha, Gi2 alpha, Gi3 alpha, and proteins from the Gq family, but no immunoreactivity toward anti-Gi1 alpha antiserum was detected. In these membranes, anti-Gs alpha antibody recognized the three cholera toxin substrates mentioned above, with the 45-kDa band displaying the highest immunoreactivity. Relative to sciatic nerve myelin, the Schwann cell membranes revealed a significantly higher expression of Gi3 alpha and the absence of Gi1 alpha. The different distribution of G proteins among the different nerve compartments might reflect the very specialized function of Schwann cells and myelin within the nerve.     

Fatty Acids from Degenerating Myelin Lipids Are Conserved and Reutilized for Myelin Synthesis During Regeneration in Peripheral Nerve

Abstract: Following nerve crush, cholesterol from degenerating myelin is conserved and reutilized for new myelin synthesis during nerve regeneration. The possibility that other myelin lipids are salvaged and reutilized has not been investigated previously. We examined the fate of myelin phospholipids and their fatty acyl moieties following nerve crush by electron microscopic autoradiography of myelin lipids prelabeled with [³H]oleate or [2-³H]-glycerol. Both precursors were incorporated predominantly (>90%) into phospholipids; >85% of the [³H]oleate was incorporated as oleate, with the remainder in longer-chain fatty acids. Before nerve crush, both labels were restricted to myelin sheaths. Following nerve crush and subsequent regeneration, over half the label from [³H]oleate, but little from [2-³H]glycerol, remained in nerve. The oleate label was present as fatty acyl moieties in phospholipids and was localized to newly formed myelin sheaths. Among the extracellular soluble lipids within the degenerating nerve, the bulk of the labeled phospholipids floated at the same density as lipoprotein particles. These data indicate that myelin phospholipids are completely hydrolyzed during nerve degeneration, that at least half the resultant free fatty acids are salvaged and reutilized for new myelin synthesis, and that these salvaged fatty acids are transported by a lipoprotein-mediated mechanism similar to that functioning in cholesterol reutilization.     

α, βI, βII, δ, and ε Protein Kinase C Isoforms and Compound Activity in the Sciatic Nerve of Normal and Diabetic Rats

Abstract: Defective protein kinase C (PKC) has been implicated in impaired Na⁺,K⁺-ATPase activity in the sciatic nerve of streptozotocin-induced diabetic rats. In the present study, α, βI, βII, γ, δ, and ε isoform-specific antibodies were used in parallel to the measurement of compound PKC activity for the characterization of PKC distribution and isoform expression in sciatic nerves of normal and diabetic rats. To distinguish isoform expression between the axonal and glial compartments, PKC isoforms were evaluated in nerves subjected to Wallerian degeneration and in a pure primary Schwann cell culture. α, βI, βII, δ, and ε but no γ isoforms were detected in sciatic nerve. Similar immunoreactivity was observed in degenerated nerves 3–4 days after transection except for diminished βI and ε species; in Schwann cell cultures, only α, βII, δ, and ε were detected. In normal nerves, two-thirds of PKC compound activity was found in the cytosol and 50% of total enzyme activity translocated to the Na⁺,K⁺-ATPase-enriched membrane fraction with phorbol myristate acetate. Similar redistribution patterns were observed for the immunoreactivity of all isoforms with the exception of δ, which did not translocate to the membrane with phorbol myristate acetate. No abnormality in compound PKC activity, in the immunoreactive intensity, or in the distribution of PKC isoforms could be detected in rat sciatic nerve after 6–12 weeks of diabetes. Thus, defective activation rather than decreased intrinsic PKC activity may occur in diabetic neuropathy.     

1,2-Diacylglycerol Content and Its Arachidonyl-Containing Molecular Species Are Reduced in Sciatic Nerve from Streptozotocin-induced Diabetic Rats

The content of 1,2-diacylglycerol (DAG) was determined in sciatic nerves from normal and streptozotocin-induced diabetic rats. In nerves frozen in situ, DAG content was reduced 22% in the proximal region and 77% in the distal region of diabetic nerve, principally because of the loss of associated fat. DAG levels in freshly dissected and desheathed diabetic nerve were decreased from 23 to 30% as compared with normal nerve. Determination of DAG molecular species distribution in desheathed normal nerve indicated that 18:0/20:4 accounted for 34%, 16:0/18:1 for 17%, and several other polyunsaturated fatty acid-containing species for 17% of the total. In diabetic nerve, the quantity of the 18:0/20:4 DAG, species was reduced by 37%, and this drop was 62% of the reduction in all molecular species. The content of the minor species, 16:0/20:4 DAG, was decreased by 48%. Our results suggest that nerve DAG arises in large part from phosphoinositide degradation. Moreover, these results provide support for the hypothesis that reduced Na+,K(+)-ATPase activity in diabetic nerve is a consequence of decreased phosphoinositide turnover, which thereby generates insufficient DAG to maintain a protein kinase C-mediated step necessary for activation of Na+,K(+)-ATPase.     

Metabolism of Phospholipids in Peripheral Nerve from Rats with Chronic Streptozotocin-induced Diabetes Increased Turnover of Phosphatidylinositol-4,5-Bisphosphate

The effect of chronic streptozotocin-induced diabetes on phospholipid metabolism in rat sciatic nerve in vitro was investigated. In normal nerve incubated for 2 h in Krebs-Ringer-bicarbonate buffer containing [32P]orthophosphate, radioactivity was primarily incorporated into phosphatidylinositol-4,5-bisphosphate and phosphatidylcholine. Smaller amounts were present in phosphatidylinositol-4-phosphate, phosphatidylinositol, and phosphatidic acid. As compared to controls, phosphatidylinositol-4,5-bisphosphate in nerves from animals made diabetic 2, 10, and 20 weeks earlier accounted for 30-46% more of the isotope, expressed as a percentage, incorporated into all phospholipids. In contrast, the proportion of radioactivity in phosphatidylcholine decreased by 10-25%. When the results were expressed as the quantity of phosphorus incorporated into phospholipid, only phosphatidylinositol-4,5-bisphosphate displayed a change. The amount of isotope which entered this lipid increased 60% and 67% for 2- and 10-week diabetic animals, respectively. Increased phosphatidylinositol-4,5-bisphosphate labeling was observed when epineurial-free preparations were used or when the composition of the incubation medium was varied. Sciatic and caudal nerve conduction velocities were decreased after 10 and 20 weeks but were unchanged after 2 weeks. We conclude that an increase in the turnover of phosphatidylinositol-4,5-bisphosphate in sciatic nerve from streptozotocin-diabetic rats appears relatively early and persists throughout the course of the disease. This metabolic alteration may be related to a primary defect responsible for the accompanying deficient peripheral nerve function.     

Myelin Basic Protein Deposition in the Optic and Sciatic Nerves of Dysmyelinating Mutants Quaking, Jimpy, Trembler, MLD, and Shiverer During Development

An ontogenetic survey of the basic protein of myelin, common to both central and peripheral nervous systems, was carried out on normal C57Bl and five dysmyelinating mutant mice. Myelin basic protein (MBP) was quantified by radioimmunoassay in the optic and sciatic nerves of mice from birth to adult stages, giving special attention to the premyelinating and early myelination periods. In the optic nerves of normal mice, MBP was already detectable at birth but the active period of myelin deposition was shown to occur after day 10 postnatal. The timing and rate of accumulation of MBP were normal in Trembler. In contrast, they were abnormal in the other mutants. In the quaking mouse, the active period of MBP deposition was delayed, and its final concentration represented no more than 12% of normal in the adult. No active period of MBP deposition was observed in the other mutants. In the jimpy mouse, a slow accumulation of MBP resulted in a final concentration reaching 2% of the normal value at 25 days. In mild and shiverer mice, the MBP was hardly detectable. In the sciatic nerves of normal mice, the active period of MBP deposition occurred between days 3 and 12 postnatal. No substantial changes occurred in the period of 2 months--2 years.(ABSTRACT TRUNCATED AT 250 WORDS)     

P0 phosphorylation in nerves from normal and diabetic rats: Role of protein kinase C and turnover of phosphate groups

The effects of phorbol ester and forskolin on the net phosphorylation and turnover of P₀ phosphate groups was studied in normal and exprimentally diabetic rats. In sciatic nerve segments isolated from normal rats and incubated with [³²P]-inorganic phosphate, phosphorylation of the major peripheral myelin protein, P₀, was increased 2–5 fold in a time and dose-dependent manner by phorbol 12,13 dibutyrate (PDB). This increase was blocked by the protein kinase inhibitors, H-7 and staurosporine. Both the basal and PDB-stimulated phosphorylation of P₀ were significantly greater in segments of sciatic nerve from streptozotocin-induced diabetic rats. Prolonged exposure of nerve segments to PDB abolished the stimulated phosphorylation of P₀ and immunoblots of nerve proteins revealed a decrease in the content of the protein kinase C -isoform. The adenylate cyclase activator, forskolin, had no affect on the PDB-stimulated phosphorylation of P₀ in normal nerve but decreased phosphorylation in diabetic nerve. To measure turnover of P₀ phosphate groups, nerves were incubated with³²P and incorporated label was then chased in radioactivity-free medium for up to 4 hours. P₀ from normal nerve prelabeled under basal conditions lost 25% of its radioactivity during this time. In contrast, nearly all of the additional phosphate groups prelabeled in the presence of PDB disappeared after 2 hours of chase. P₀ phosphate groups from diabetic nerve displayed similar turnover kinetics. When forskolin was added to the chase medium, the turnover of P₀ phosphate moieties was accelerated in normal, but not in diabetic nerve. These findings clearly establish a prominent role for protein kinase C in P₀ phosphorylation, provide evidence for heterogeneous turnover of P₀ phosphate groups and suggest that cyclic AMP-mediated processes may modulate P₀ phosphorylation. Further, these results indicate that the metabolism of P₀ phosphate moieties is perturbed in nerve from diabetic animals.Special issue dedicated to Dr. Marjoris B. Lees.     

Lipid Metabolism in Peripheral Nerve Cell Culture (Rich in Schwann Cells) from Normal and Trembler Mice

Abstract: A culture of peripheral nerve cells, very rich in Schwann cells, was developed from sciatic nerve. In both normal and Trembler, typical spindle-shaped cells were seen; most of the cells were surrounded by basement membrane-like material (predominantly in-between adjacent cells). In Trembler cells, cultivated in the presence of labelled acetate, the fatty acids were slightly altered; phosphatidylcholine was slightly reduced and phosphatidyl-ethanolamine increased. Sulfatides were increased four times.     

糖尿病病理性神经痛大鼠坐骨神经中miR-133a的上调对疼痛阈值的影响及机制

摘要 目的：探究糖尿病病理性神经痛大鼠坐骨神经中miR-133a的上调对疼痛阈值的影响及机制。方法：使用NGS测序和定量PCR分析糖尿病病理性神经痛大鼠坐骨神经中的相关 miRNA表达,预测潜在下游目标。使用miR-133a-3p转染的 RSC96细胞进行体外实验。使用微蛋白质印迹和蛋白质印迹以及免疫荧光分析验证miR-133a-3p的作用。使用miR-133a-3p拮抗剂分析miR-133a-3p与DNP之间的关联。结果：miR-133a-3p模拟物增加了RSC96细胞中VEGFR-2、p38αMAPK、TRAF-6和PIAS3的表达,并降低了NFκB p50和MKP3的表达（P＜0.05）。在正常大鼠中,AAV-miR-133a-3p通过神经内注射到坐骨神经中可诱导机械性异常性疼痛和p-p38 MAPK激活（P＜0.05）。在DM大鼠中,miR-133a-3p 拮抗剂给药可减轻DNP并下调p-p38磷酸化（P＜0.05）。结论：坐骨神经中miR-133a-3p的过度表达会引起这种疼痛,miR-133a-3p可能是患有神经性疼痛的患者的有用治疗靶点。     

Inhibition of Protein Kinase C Restores Na+, K+-ATPase Activity in Sciatic Nerve of Diabetic Mice

We have tested if inhibition of protein kinase C is able to prevent and/or to restore the decrease of Na+,K(+)-ATPase activity in the sciatic nerve of alloxan-induced diabetic mice. Mice were made diabetic by subcutaneous injection of 200 mg of alloxan/kg of body weight. The activity of Na+,K(+)-ATPase decreased rapidly (43% after 3 days) and slightly thereafter (58% at 11 days). We show that intraperitoneal injection of 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H7), an inhibitor of protein kinase C, prevents completely the loss of Na+,K(+)-ATPase activity produced by alloxan. Also, H7 injected into diabetic mice, 4-9 days after the injection of alloxan, restores the activity of the enzyme. The amount of activity recovered depends on the dose of H7 administered; complete recovery was reached with injection of 15 mg of H7/kg of body weight. The effect of H7 is transient, with a half-life of approximately 1 h.     

补阳还五汤联合针灸对糖尿病周围神经病变患者血糖代谢、神经传导速度和血液流变学的影响

摘要 目的：探讨补阳还五汤联合针灸对糖尿病周围神经病变（DPN）患者血糖代谢、神经传导速度和血液流变学的影响。方法：选取我院2018年4月-2021年4月期间收治的100例DPN患者,按照双色球法将患者分为对照组（50例,常规西医治疗）和研究组（50例,对照组基础上接受补阳还五汤联合针灸治疗）。均治疗4周,对比两组临床疗效、血糖代谢水平、神经传导速度和血液流变学。结果：治疗后研究组临床总有效率（94.00%）,高于对照组（72.00%）（P<0.05）。治疗后研究组的空腹血糖（FPG）、餐后2 h血糖（2hPG）、糖化血红蛋白（HbA1c）水平均低于对照组（P<0.05）。治疗后研究组的腓总神经和正中神经感觉神经传导速度（SNCV）、运动神经传导速度（MNCV）均较对照组高（P<0.05）。治疗后研究组的红细胞比积、纤维蛋白原、全血粘度（高切）及全血粘度（低切）水平均低于对照组（P<0.05）。结论：补阳还五汤联合针灸治疗DPN患者疗效显著,有效提高其神经传导速度,改善其血糖代谢和血液流变学。     

"标本配穴"针灸结合甲钴胺对老年糖尿病周围神经病变患者糖脂代谢、炎性细胞因子和受损神经传导速度的影响

摘要 目的：探讨"标本配穴"针灸结合甲钴胺对老年糖尿病周围神经病变（DPN）患者糖脂代谢、炎性细胞因子和受损神经传导速度的影响。方法：选取2018年3月~2019年12月期间我院收治的93例老年DPN患者，按照随机数字表法将患者分为研究组（n=47）、对照组（n=46），对照组患者予以甲钴胺治疗，研究组在对照组的基础上联合"标本配穴"针灸治疗，比较两组疗效、糖脂代谢、炎性细胞因子、受损神经传导速度及不良反应。结果：研究组治疗4周后的临床总有效率87.23%（41/47）高于对照组69.57%（32/46）（P<0.05）。两组治疗4周后空腹血糖（FPG）、甘油三酯（TG）、总胆固醇（TC）、糖化血红蛋白（HbAlc）均下降，且研究组低于对照组（P<0.05）。两组治疗4周后白介素-6（IL-6）、白介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）均下降，且研究组低于对照组（P<0.05）。两组治疗4周后腓总神经运动神经传导速度（MCV）、正中神经MCV、腓总神经感觉神经传导速度（SCV）、正中神经SCV均升高，且研究组高于对照组（P<0.05）。两组均未见明显不良反应发生。结论："标本配穴"针灸结合甲钴胺治疗老年DPN患者疗效确切，可改善患者糖脂代谢、炎性细胞因子和受损神经传导速度，安全可靠。     

Differential Ultrastructural Localization of Myelin Basic Protein, Myelin/Oligodendroglial Glycoprotein, and 2'',3''-Cyclic Nucleotide 3''-Phosphodiesterase in the CNS of Adult Rats

In a light and electron microscopic immunocytochemical study we have examined the distribution of myelin basic protein (MBP), 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP), and myelin/oligodendroglial glycoprotein (MOG) within CNS myelin sheaths and oligodendrocytes of adult Sprague-Dawley rats. Ultrastructural immunocytochemistry allowed quantitative analysis of antigen density in different myelin and oligodendrocyte zones: MBP was detectable in high density over the whole myelin sheath, but not in regions of loops, somata, or the oligodendrocyte plasma membrane. CNP reactivity was highest at the myelin/axon interface, and found in lower concentration over the outer lamellae of myelin sheaths, at the cytoplasmic face of oligodendrocyte membranes, and throughout the compact myelin. MOG was preferentially detected at the extracellular surface of myelin sheaths and oligodendrocytes and in only low amounts in the lamellae of compacted myelin and the myelin/axon border zone. Our studies, thus, indicate further the presence of different molecular domains in compact myelin, which may be functionally relevant for the integrity and maintenance of the myelin sheath.     

Effects of Nigella sativa and its Major Constituent, Thymoquinone on Sciatic Nerves in Experimental Diabetic Neuropathy

The aim of this study was designed to investigate the possible beneficial effects of Nigella sativa (NS) and thymoquinone (TQ) on histopathological changes of sciatic nerves in streptozotocin-induced diabetic rats. The rats were randomly allotted into one of four experimental groups: A (control), B (diabetic untreated), C (diabetic treated with NS) and D (diabetic treated with TQ); each group contain ten animals. B, C and D groups received streptozotocin (STZ) to induce diabetes. The rats in NS and TQ treated groups were given NS (in a dose of 400 mg/kg body weight) and TQ (50 mg/kg body weight) once a day orally by using intra-gastric intubation for 12 weeks starting 2 days after STZ injection, respectively. Blood and tissue samples were obtained for biochemical and histopathological investigation. The treatment of both NS and TQ caused a sharp decrease in the elevated serum glucose (P < 0.01, 0.05, respectively), and an increase in the lowered serum insulin concentrations (P < 0.01, 0.05, respectively), in STZ-induced diabetic rats. STZ induced a significant decrease in the area of insulin immunoreactive β-cells (P < 0.0001). NS (P < 0.001) and TQ (P < 0.01) treatment resulted in increased area of insulin immunoreactive β-cells significantly. To date, no histopathological changes of sciatic nerves in STZ induced diabetic rats by NS and TQ treatment have been reported. In this study, histologic evaluation of the tissues in diabetic animals treated with TQ and especially NS showed fewer morphologic alterations. Myelin breakdown decreased significantly after treatment with NS and TQ. The ultrastructural features of axons also showed remarkable improvement. We believe that further preclinical research into the utility of NS and TQ may indicate its usefulness as a potential treatment on peripheral neuropathy (PN) in STZ induced diabetic rats.