Membrane-associated microtubular areays induced in proximal myelinated processes of dorsal root ganglia by large doses of vitamin B6

Author(s):  
V.J. Montpetit ◽  
S. Dancea ◽  
L. Tryphonas ◽  
D.F. Clapin

Very large doses of pyridoxine (vitamin B6) are neurotoxic in humans, selectively affecting the peripheral sensory nerves. We have undertaken a study of the morphological and biochemical aspects of pyridoxine neurotoxicity in an animal model system. Early morphological changes in dorsal root ganglia (DRG) associated with pyridoxine megadoses include proliferation of neurofilaments, ribosomes, rough endoplasmic reticulum, and Golgi complexes. We present in this report evidence of the formation of unique aggregates of microtubules and membranes in the proximal processes of DRG which are induced by high levels of pyridoxine.

Cell Reports ◽  
2018 ◽  
Vol 25 (2) ◽  
pp. 271-277.e4 ◽  
Author(s):  
Chaitanya K. Gavini ◽  
Angie L. Bookout ◽  
Raiza Bonomo ◽  
Laurent Gautron ◽  
Syann Lee ◽  
...  

2018 ◽  
Vol 29 (13) ◽  
pp. 1640-1651 ◽  
Author(s):  
Haifang Zhao ◽  
Jing Wang ◽  
Tao Wang

Synthesis and maturation of the light sensor, rhodopsin, are critical for the maintenance of light sensitivity and for photoreceptor homeostasis. In Drosophila, the main rhodopsin, Rh1, is synthesized in the endoplasmic reticulum and transported to the rhabdomere through the secretory pathway. In an unbiased genetic screen for factors involved in rhodopsin homeostasis, we identified mutations in vha68-1, which encodes the vacuolar proton-translocating ATPase (V-ATPase) catalytic subunit A isoform 1 of the V1 component. Loss of vha68-1 in photoreceptor cells disrupted post-Golgi anterograde trafficking of Rh1, reduced light sensitivity, increased secretory vesicle pH, and resulted in incomplete Rh1 deglycosylation. In addition, vha68-1 was required for activity-independent photoreceptor cell survival. Importantly, vha68-1 mutants exhibited phenotypes similar to those exhibited by mutations in the V0 component of V-ATPase, vha100-1. These data demonstrate that the V1 and V0 components of V-ATPase play key roles in post-Golgi trafficking of Rh1 and that Drosophila may represent an important animal model system for studying diseases associated with V-ATPase dysfunction.


1955 ◽  
Vol 1 (1) ◽  
pp. 69-88 ◽  
Author(s):  
Sanford L. Palay ◽  
George E. Palade

1. Thin sections of representative neurons from intramural, sympathetic and dorsal root ganglia, medulla oblongata, and cerebellar cortex were studied with the aid of the electron microscope. 2. The Nissl substance of these neurons consists of masses of endoplasmic reticulum showing various degrees of orientation; upon and between the cisternae, tubules, and vesicles of the reticulum lie clusters of punctate granules, 10 to 30 mµ in diameter. 3. A second system of membranes can be distinguished from the endoplasmic reticulum of the Nissl bodies by shallower and more tightly packed cisternae and by absence of granules. Intermediate forms between the two membranous systems have been found. 4. The cytoplasm between Nissl bodies contains numerous mitochondria, rounded lipid inclusions, and fine filaments.


2021 ◽  
Author(s):  
Thanh T Le ◽  
Samantha L Payne ◽  
Maia N Buckwald ◽  
Lily A Hayes ◽  
Christopher B Burge ◽  
...  

AbstractIn breast cancer, nerve presence has been correlated with more invasive disease and worse prognosis, yet the mechanisms by which different types of peripheral nerves drive tumor progression remain poorly understood. In this study, we identified sensory nerves as more abundant in human triple-negative breast cancer (TNBC) tumors. Coinjection of sensory neurons isolated from the dorsal root ganglia (DRG) of adult female mice with human TNBC cells in immunocompromised mice increased the number of lung metastases. Direct in vitro co-culture of human TNBC cells with the dorsal root ganglia (DRG) of adult female mice revealed that TNBC cells adhere to sensory neuron fibers leading to an increase in migration speed. Species-specific RNA sequencing revealed that co-culture of TNBC cells with sensory nerves upregulates the expression of genes associated with cell migration and adhesion in cancer cells. We demonstrate that the axon guidance molecule Plexin B3 mediates cancer cell adhesion to and migration on sensory nerves. Together, our results identify a novel mechanism by which nerves contribute to breast cancer migration and metastasis by inducing a shift in TNBC cell gene expression and support the rationale for disrupting neuron-cancer cell interactions to target metastasis.SignificanceThe presence of nerves in breast tumors has been associated with poor outcome. Understanding the mechanisms by which nerves contribute to tumor progression could help identify novel strategies to target metastatic disease.


2009 ◽  
Vol 111 (2) ◽  
pp. 393-405 ◽  
Author(s):  
Geza Gemes ◽  
Marcel Rigaud ◽  
Paul D. Weyker ◽  
Stephen E. Abram ◽  
Dorothee Weihrauch ◽  
...  

Background Painful nerve injury leads to disrupted Ca signaling in primary sensory neurons, including decreased endoplasmic reticulum (ER) Ca storage. This study examines potential causes and functional consequences of Ca store limitation after injury. Methods Neurons were dissociated from axotomized fifth lumbar (L5) and the adjacent L4 dorsal root ganglia after L5 spinal nerve ligation that produced hyperalgesia, and they were compared to neurons from control animals. Intracellular Ca levels were measured with Fura-2 microfluorometry, and ER was labeled with probes or antibodies. Ultrastructural morphology was analyzed by electron microscopy of nondissociated dorsal root ganglia, and intracellular electrophysiological recordings were obtained from intact ganglia. Results Live neuron staining with BODIPY FL-X thapsigargin (Invitrogen, Carlsbad, CA) revealed a 40% decrease in sarco-endoplasmic reticulum Ca-ATPase binding in axotomized L5 neurons and a 34% decrease in L4 neurons. Immunocytochemical labeling for the ER Ca-binding protein calreticulin was unaffected by injury. Total length of ER profiles in electron micrographs was reduced by 53% in small axotomized L5 neurons, but it was increased in L4 neurons. Cisternal stacks of ER and aggregation of ribosomes occurred less frequently in axotomized neurons. Ca-induced Ca release, examined by microfluorometry with dantrolene, was eliminated in axotomized neurons. Pharmacologic blockade of Ca-induced Ca release with dantrolene produced hyperexcitability in control neurons, confirming its functional importance. Conclusions After axotomy, ER Ca stores are reduced by anatomic loss and possibly diminished sarco-endoplasmic reticulum Ca-ATPase. The resulting disruption of Ca-induced Ca release and protein synthesis may contribute to the generation of neuropathic pain.


2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Luisa Muratori ◽  
Giulia Ronchi ◽  
Stefania Raimondo ◽  
Stefano Geuna ◽  
Maria Giuseppina Giacobini-Robecchi ◽  
...  

The evidence of neurons generatedex novoin sensory ganglia of adult animals is still debated. In the present study, we investigated, using high resolution light microscopy and stereological analysis, the changes in the number of neurons in dorsal root ganglia after 30 days from a crush lesion of the rat brachial plexus terminal branches. Results showed, as expected, a relevant hypertrophy of dorsal root ganglion neurons. In addition, we reported, for the first time in the literature, that neuronal hypertrophy was accompanied by massive neuronal hyperplasia leading to a 42% increase of the number of primary sensory neurons. Moreover, ultrastructural analyses on sensory neurons showed that there was not a relevant neuronal loss as a consequence of the nerve injury. The evidence of BrdU-immunopositive neurons and neural progenitors labeled with Ki67, nanog, nestin, and sox-2 confirmed the stereological evidence of posttraumatic neurogenesis in dorsal root ganglia. Analysis of morphological changes following axonal damage in addition to immunofluorescence characterization of cell phenotype suggested that the neuronal precursors which give rise to the newly generated neurons could be represented by satellite glial cells that actively proliferate after the lesion and are able to differentiate toward the neuronal lineage.


1966 ◽  
Vol 31 (2) ◽  
pp. 215-242 ◽  
Author(s):  
Miro Brzin ◽  
Virginia M. Tennyson ◽  
Philip E. Duffy

The localization and chemical determination of acetylcholin esterase in the frog sympathetic and dorsal root ganglia were studied by a combination of the methods of electron microscopy, histochemistry, and microgasometric analysis with the magnetic diver. The Koelle-Friedenwald copper thiocholine histochemical method was modified by eliminating the sulfide conversion and by treatment of the tissue with potassium permanganate. In fixed tissue, enzymatic activity was demonstrated on the inner surface of the endoplasmic reticulum, nuclear envelope, subsurface cisternae, and agranular reticulum of the perikaryon and axon. In briefly fixed tissue, end product appeared also at the axon-sheath and the sheath-sheath interface. Activity at the synaptic junction was most readily obtained in unfixed tissue. Isolated neurons recovered from the diver following chemical analysis were studied with the electron microscope. Cells having a high enzyme activity showed a badly ruptured or absent neural plasmalemma and sheath. In this case the measured activity was apparently due to the enzyme present in the endoplasmic reticulum. Neurons having low activity exhibited an intact plasmalemma and sheath. This may reflect the effectiveness of the neural plasmalemma and sheath as a penetration barrier. The effects of fixation on enzyme activity are discussed. Electron microscopic examination of cells following microgasometric analysis is shown to be essential for the interpretation of the biochemical data.


1971 ◽  
Vol 50 (3) ◽  
pp. 859-886 ◽  
Author(s):  
Phyllis M. Novikoff ◽  
Alex B. Novikoff ◽  
Nelson Quintana ◽  
Jean-Jacques Hauw

New insights into the ultrastructure and phosphatase localizations of Golgi apparatus and GERL, and into the probable origin of lysosomes in the neurons of fetal dorsal root ganglia and the small neurons of adult ganglia have come from studying thick (0.5–1.0 µ) as well as thin (up to 500 A) sections by conventional electron microscopy. Tilting the thick specimens, by a goniometer stage, has helped to increase our understanding of the three-dimensional aspects of the Golgi apparatus and GERL. One Golgi element, situated at the inner aspect of the Golgi stack, displays thiamine pyrophosphatase and nucleoside diphosphatase activities. This element exhibits regular geometric arrays (hexagons) of interconnected tubules without evidence of a flattened portion (saccule or cisterna). In contrast, GERL shows acid phosphatase activity and possesses small cisternal portions and anastomosing tubules. Lysosomes appear to bud from GERL. Osmium deposits, following prolonged osmication, are found in the outer Golgi element. Serial 0.5-µ and thin sections of thiamine pyrophosphatase-incubated material demonstrate that, in the neurons studied, the Golgi apparatus is a continuous network coursing through the cytoplasm. Serial thick sections of acid phosphatase-incubated tissue suggest that GERL is also a continuous structure throughout the cytoplasm. Tubules of smooth endoplasmic reticulum, possibly part of GERL, extend into the polygonal compartments of the inner Golgi element. The possible physiological significance of a polygonal arrangement of a phosphatase-rich Golgi element in proximity to smooth ER is considered. A tentative diagram of the Golgi stack and associated endoplasmic reticulum in these neurons has been drawn.


2020 ◽  
Author(s):  
Yuan Li ◽  
Heng Zhang ◽  
Ning-Tao Ren ◽  
Chao Chen ◽  
Peng Qi ◽  
...  

Abstract Background: Previous studies demonstrate that long-tern microgravity induces multi-organ injury and dysfunction, including the dorsal root ganglia (DRG) damage. This study investigated oral pyruvate protective effects on lumbar 5 (L5) DRG nerve tissues in rats subjected to hindlimb unweighting (HU).Results: Male Sprague-Dawley rats were randomly assigned to four groups (n=10): control group (Group CON), suspension group (Group SUS), normal saline group (Group SAL) and sodium pyruvate group (Group PYR), respectively. The rats of SUS, SAL and PYR groups were simulated with microgravity by tail suspension of HU for 8 weeks. Rats in Groups SAL and PYR fed with normal saline and pyruvate saline, respectively. Histopathological and immunofluorescence examinations were conducted and levels of glial cell line-derived neurotrophic factor (GDNF), glial fibrillary acidic protein (GFAP), ATP and ATPase were measured in DRG tissues; L5 spinal cord scans were also carried out in rats following HU. Results showed that the HU resulted in significant alterations in DRG nerve tissues’ structure and function in Groups SUS and SAL, whereas morphological changes were not significantly distinguished between Group PYR and Group CON; GDNF, GFAP, ATP and ATPase levels were mostly preserved in Group PYR, but still worse than in Group CON. The significance of oral pyruvate protection against DRG injury following HU and the dose and formula of oral pyruvate solutions were discussed for use in astronauts’ spaceflight.Conclusions: oral pyruvate effectively protected L5 DRG from pathological alterations and dysfunction induced by the HU in rats. Further studies and clinical trials are warranted.


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