Development of Selective Axonopathy in Adult Sensory Neurons Isolated From Diabetic Rats

Zherebitskaya, Elena; Akude, Eli; Smith, Daniel R.; Fernyhough, Paul

doi:10.2337/db09-0034

Cited by 142 publications

(143 citation statements)

References 43 publications

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“…It has been suggested that internal ribosomal initiation of mRNA translation, a step that is affected by rapamycin and p70S6K, is critical for survival of cells under transient apoptotic stress ( 107 ). Postmitotic neurons require protein synthesis for survival ( 108 ) so it is possible that insulin stimulates protein synthesis via a rapamycin-dependent ture, are consistent with reports showing impaired axonal growth and aberrant dystrophic structures in dorsal root ganglion neurons from diabetic animals and in neurons cultured under high glucose conditions ( 154,155 ).…”

Section: Protein Tyrosine Phosphatase-1b and Pi3k Pathwaysupporting

confidence: 60%

Phosphoinositide 3-kinase signaling in the vertebrate retina

Rajala

2010

Journal of Lipid Research

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This article is available online at http://www.jlr.org was established by Streb et al. ( 3 ) in their classic paper that showed elevations in IP 3 caused intracellular release of bound calcium. Subsequently, 1,2-DG was found to stimulate protein kinase C (PKC), a serine/threonine kinase that phosphorylates a number of cellular proteins ( 4 ). Activation of the PLC/PKC cascade affects a variety of cellular events, including secretion, phagocytosis, smooth muscle contraction, proliferation, neurotransmission, and metabolism [see reviews by Rhee ( 5 ), Rhee and Choi ( 6 ), and Berridge ( 7 ) THE PI CYCLEIn the early 1950s, Hokin and Hokin ( 1, 2 ) discovered that addition of acetylcholine to brain slices stimulated the incorporation of phosphate and inositol but not glycerol into lipids; the major products of this incorporation were phosphatidylinositol (PI) and phosphatidic acid. Subsequent studies defi ned the reactions of the PI cycle and showed that the initial event was receptor-meditated activation of a phospholipase C (PLC), which hydrolyzes phosphatidylinositol 4,5-bisphosphate (PI-4,5-P 2 ) to 1,2-diacylglycerol (DG) and inositol 1,4,5-trisphosphate (IP 3 ). This increase in lipid synthesis reported by the Hokins was a recovery reaction that rapidly replenished PI separate from de novo PI synthesis. The role of 1,4, This work was supported by grants

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Section: Protein Tyrosine Phosphatase-1b and Pi3k Pathwaysupporting

confidence: 60%

Phosphoinositide 3-kinase signaling in the vertebrate retina

Rajala

2010

Journal of Lipid Research

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“…Neurons derived from STZ-induced diabetic rodents exhibited oxidative stress, reduced spare respiratory capacity, and when dissociated and placed in culture, impaired neurite outgrowth (4,11,35). Spare respiratory capacity was increased in these neurons by the M 1 R antagonists MT7 (100 nM, in STZ-mouse DRG culture) ( Figure 3B and Supplemental Figure 4B), VU0255035 (10 μM, in STZ-rat DRG culture), or pirenzepine (1 μM, in STZ-mouse DRG culture) (Supplemental Figure 4D).…”

Section: Resultsmentioning

confidence: 99%

Selective antagonism of muscarinic receptors is neuroprotective in peripheral neuropathy

Calcutt¹,

Smith²,

Frizzi³

et al. 2017

Journal of Clinical Investigation

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“…In this model, dendritic beading and axonal swellings were prominent, and neuronal process degeneration appeared to account for the severe clinical disease and fatal outcome. The axonal swellings exhibited striking morphological similarities to the neurodegenerative changes that occur in the axons of neurons in diabetic sensory and autonomic neuropathy and in human immunodeficiency virus (HIV) infection (4,12,24,35). Studies of cultured adult dorsal root ganglion (DRG) sensory neurons from type 1 diabetic rats have revealed that glucose-induced oxidative stress is a key instigator of axonal swellings (35).…”

mentioning

confidence: 99%

Role of Oxidative Stress in Rabies Virus Infection of Adult Mouse Dorsal Root Ganglion Neurons

Jackson

Kammouni

Zherebitskaya

et al. 2010

J Virol

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Rabies virus infection of dorsal root ganglia (DRG) was studied in vitro with cultured adult mouse DRG neurons. Recent in vivo studies of transgenic mice that express the yellow fluorescent protein indicate that neuronal process degeneration, involving both dendrites and axons, occurs in mice infected with the challenge virus standard (CVS) strain of rabies virus by footpad inoculation. Because of the similarities of the morphological changes in experimental rabies and in diabetic neuropathy and other diseases, we hypothesize that neuronal process degeneration occurs as a result of oxidative stress. DRG neurons were cultured from adult ICR mice. Two days after plating, they were infected with CVS. Immunostaining was evaluated with CVS-and mock-infected cultures for neuron specific ␤-tubulin, rabies virus antigen, and amino acid adducts of 4-hydroxy-2-nonenal (4-HNE) (marker of lipid peroxidation and hence oxidative stress). Neuronal viability (by trypan blue exclusion), terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining, and axonal growth were also assessed with the cultures. CVS infected 33 to 54% of cultured DRG neurons. Levels of neuronal viability and TUNEL staining were similar in CVS-and mock-infected DRG neurons. There were significantly more 4-HNE-labeled puncta at 2 and 3 days postinfection in CVS-infected cultures than in mock-infected cultures, and axonal outgrowth was reduced at these time points in CVS infection. Axonal swellings with 4-HNE-labeled puncta were also associated with aggregations of actively respiring mitochondria. We have found evidence that rabies virus infection in vitro causes axonal injury of DRG neurons through oxidative stress. Oxidative stress may be important in vivo in rabies and may explain previous observations of the degeneration of neuronal processes.Rabies is an acute viral infection of the central nervous system (CNS) that is usually fatal in humans and animals (10). Despite its lethality, under natural conditions only relatively mild histopathological lesions are typically found in association with a paucity of degenerative neuronal changes (9, 21). Li et al. (13) showed severe destruction and disorganization of axons and disruption of synaptic structures in silver-stained hippocampal sections from mice infected intracerebrally with the pathogenic N2C strain of rabies virus. Infection with the challenge virus standard (CVS) strain of rabies virus has recently been evaluated using hindlimb footpad inoculation in adult transgenic mice expressing yellow fluorescent protein (26). In this model, dendritic beading and axonal swellings were prominent, and neuronal process degeneration appeared to account for the severe clinical disease and fatal outcome. The axonal swellings exhibited striking morphological similarities to the neurodegenerative changes that occur in the axons of neurons in diabetic sensory and autonomic neuropathy and in human immunodeficiency virus (HIV) infection (4,12,24,35). Studies of cultured adult dorsal root ganglio...

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Development of Selective Axonopathy in Adult Sensory Neurons Isolated From Diabetic Rats

Cited by 142 publications

References 43 publications

Phosphoinositide 3-kinase signaling in the vertebrate retina

Phosphoinositide 3-kinase signaling in the vertebrate retina

Selective antagonism of muscarinic receptors is neuroprotective in peripheral neuropathy

Role of Oxidative Stress in Rabies Virus Infection of Adult Mouse Dorsal Root Ganglion Neurons

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