scholarly journals Protective Effect of Magnesium-25 Carrying Porphyrin-Fullerene Nanoparticles on Degeneration of Dorsal Root Ganglion Neurons and Motor Function in Experimental Diabetic Neuropathy

2011 ◽  
Vol 109 (5) ◽  
pp. 381-386 ◽  
Author(s):  
Asieh Hosseini ◽  
Mohammad Abdollahi ◽  
Gholamreza Hassanzadeh ◽  
Mahdi Rezayat ◽  
Shokoufeh Hassani ◽  
...  
Keyword(s):  
Dorsal Root Ganglion ◽  
Diabetic Neuropathy ◽  
Protective Effect ◽  
Motor Function ◽  
Dorsal Root ◽  
Dorsal Root Ganglion Neurons ◽  
Fullerene Nanoparticles ◽  
Ganglion Neurons ◽  
Experimental Diabetic Neuropathy

scholarly journals Overexpression of Sirtuin 1 protein in neurons prevents and reverses experimental diabetic neuropathy

Brain ◽  
2019 ◽  
Vol 142 (12) ◽  
pp. 3737-3752 ◽  
Author(s):  
Krish Chandrasekaran ◽  
Mohammad Salimian ◽  
Sruthi R Konduru ◽  
Joungil Choi ◽  
Pranith Kumar ◽  
...  
Keyword(s):  
Dorsal Root Ganglion ◽  
Diabetic Neuropathy ◽  
Dorsal Root ◽  
Axonal Growth ◽  
Dorsal Root Ganglion Neurons ◽  
Sirtuin 1 ◽  
Wild Type ◽  
Respiratory Capacity ◽  
Ganglion Neurons ◽  
Experimental Diabetic Neuropathy

Abstract In diabetic neuropathy, there is activation of axonal and sensory neuronal degeneration pathways leading to distal axonopathy. The nicotinamide-adenine dinucleotide (NAD+)-dependent deacetylase enzyme, Sirtuin 1 (SIRT1), can prevent activation of these pathways and promote axonal regeneration. In this study, we tested whether increased expression of SIRT1 protein in sensory neurons prevents and reverses experimental diabetic neuropathy induced by a high fat diet (HFD). We generated a transgenic mouse that is inducible and overexpresses SIRT1 protein in neurons (nSIRT1OE Tg). Higher levels of SIRT1 protein were localized to cortical and hippocampal neuronal nuclei in the brain and in nuclei and cytoplasm of small to medium sized neurons in dorsal root ganglia. Wild-type and nSIRT1OE Tg mice were fed with either control diet (6.2% fat) or a HFD (36% fat) for 2 months. HFD-fed wild-type mice developed neuropathy as determined by abnormal motor and sensory nerve conduction velocity, mechanical allodynia, and loss of intraepidermal nerve fibres. In contrast, nSIRT1OE prevented a HFD-induced neuropathy despite the animals remaining hyperglycaemic. To test if nSIRT1OE would reverse HFD-induced neuropathy, nSIRT1OE was activated after mice developed peripheral neuropathy on a HFD. Two months after nSIRT1OE, we observed reversal of neuropathy and an increase in intraepidermal nerve fibre. Cultured adult dorsal root ganglion neurons from nSIRT1OE mice, maintained at high (30 mM) total glucose, showed higher basal and maximal respiratory capacity when compared to adult dorsal root ganglion neurons from wild-type mice. In dorsal root ganglion protein extracts from nSIRT1OE mice, the NAD+-consuming enzyme PARP1 was deactivated and the major deacetylated protein was identified to be an E3 protein ligase, NEDD4-1, a protein required for axonal growth, regeneration and proteostasis in neurodegenerative diseases. Our results indicate that nSIRT1OE prevents and reverses neuropathy. Increased mitochondrial respiratory capacity and NEDD4 activation was associated with increased axonal growth driven by neuronal overexpression of SIRT1. Therapies that regulate NAD+ and thereby target sirtuins may be beneficial in human diabetic sensory polyneuropathy.

scholarly journals TNF-α mediated upregulation of NaV1.7 currents in rat dorsal root ganglion neurons is independent of CRMP2 SUMOylation

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Flávio Henrique Pequeno de Macedo ◽  
Rosária Dias Aires ◽  
Esdras Guedes Fonseca ◽  
Renata Cristina Mendes Ferreira ◽  
Daniel Portela Dias Machado ◽  
...  
Keyword(s):  
Dorsal Root Ganglion ◽  
Diabetic Neuropathy ◽  
Dorsal Root ◽  
Sodium Current ◽  
Dorsal Root Ganglion Neurons ◽  
Drg Neurons ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Ganglion Neurons ◽  
Total Sodium

AbstractClinical and preclinical studies have shown that patients with Diabetic Neuropathy Pain (DNP) present with increased tumor necrosis factor alpha (TNF-α) serum concentration, whereas studies with diabetic animals have shown that TNF-α induces an increase in NaV1.7 sodium channel expression. This is expected to result in sensitization of nociceptor neuron terminals, and therefore the development of DNP. For further study of this mechanism, dissociated dorsal root ganglion (DRG) neurons were exposed to TNF-α for 6 h, at a concentration equivalent to that measured in STZ-induced diabetic rats that developed hyperalgesia. Tetrodotoxin sensitive (TTXs), resistant (TTXr) and total sodium current was studied in these DRG neurons. Total sodium current was also studied in DRG neurons expressing the collapsin response mediator protein 2 (CRMP2) SUMO-incompetent mutant protein (CRMP2-K374A), which causes a significant reduction in NaV1.7 membrane cell expression levels. Our results show that TNF-α exposure increased the density of the total, TTXs and TTXr sodium current in DRG neurons. Furthermore, TNF-α shifted the steady state activation and inactivation curves of the total and TTXs sodium current. DRG neurons expressing the CRMP2-K374A mutant also exhibited total sodium current increases after exposure to TNF-α, indicating that these effects were independent of SUMOylation of CRMP2. In conclusion, TNF-α sensitizes DRG neurons via augmentation of whole cell sodium current. This may underlie the pronociceptive effects of TNF-α and suggests a molecular mechanism responsible for pain hypersensitivity in diabetic neuropathy patients.

Modulation of P2X receptors in dorsal root ganglion neurons of streptozotocin-induced diabetic neuropathy

2009 ◽  
Vol 452 (2) ◽  
pp. 200-203 ◽  
Author(s):  
Keisuke Migita ◽  
Tomoko Moriyama ◽  
Masako Koguchi ◽  
Kenji Honda ◽  
Takeshi Katsuragi ◽  
...  
Keyword(s):  
Dorsal Root Ganglion ◽  
Diabetic Neuropathy ◽  
Dorsal Root ◽  
P2x Receptors ◽  
Dorsal Root Ganglion Neurons ◽  
Ganglion Neurons

scholarly journals Rolipram and Pentoxifylline Combination Ameliorates Experimental Diabetic Neuropathy Through Inhibition of Oxidative Stress and Inflammatory Pathways in the Dorsal Root Ganglion Neurons

2022 ◽  
Author(s):  
Mona Dastgheib ◽  
Seyed Vahid Shetab-Boushehri ◽  
Maryam Baeeri ◽  
Mahdi Gholami ◽  
Mohammad Yahya Karimi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dorsal Root Ganglion ◽  
Diabetic Neuropathy ◽  
Motor Function ◽  
Dorsal Root ◽  
Camp Level ◽  
Inflammatory Factors ◽  
Drg Neurons ◽  
Inflammatory Pathways ◽  
Ganglion Neurons

Abstract Diabetic neuropathy (DN) is the most challenging microvascular complication of diabetes and there is no suitable treatment for it, so the development of new agents to relieve DN is urgently needed. Since oxidative stress and inflammation play an essential role in the development of DN, clearance of these factors are good strategies for the treatment of this disease. According to key role of cyclic adenosine monophosphate (cAMP) in the regulation of oxidative stress and inflammatory pathways, it seems that phosphodiesterase inhibitors (PDEIs) can be as novel drug targets for improving DN through enhancement of cAMP level. The aim of this study was to evaluate the effects of rolipram, a selective PDE4 inhibitor, and pentoxifylline, a general PDE inhibitor on experimental model of DN and also to determine the possible mechanisms involved in the effectiveness of these agents. We investigated the effects of rolipram (1mg/kg) and pentoxifylline (100 mg/kg) and also combination of rolipram (0.5 mg/kg) and pentoxifylline (50 mg/kg), orally for five weeks in rats that became diabetic by STZ (55 mg/kg, i.p.). After treatments, motor function was evaluated by open-field test, then rats were anesthetized and dorsal root ganglion (DRG) neurons isolated. Next, oxidative stress biomarkers and inflammatory factors were assessed by biochemical and ELISA methods, and RT-PCR analysis in DRG neurons. Rolipram and/or pentoxifylline treatment significantly attenuated DN – induced motor function deficiency by modulating distance moved and velocity. Rolipram and/or pentoxifylline treatment dramatically increased the cAMP level, as well as suppressed DN – induced oxidative stress which was associated with decrease in LPO and ROS and increase in TAC, total thiol, CAT and SOD in DRG neurons. On the other hand, the level of inflammatory factors (TNF-α, NF-kB and COX2) significantly decreased following rolipram and/or pentoxifylline administration.The maximum effectiveness was with rolipram and/or pentoxifylline combination on mentioned factors.These findings provide novel experimental evidence for further clinical investigations on rolipram and pentoxifylline combination for the treatment of DN.

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