The Schwann Cell-Axon Link in Normal Condition or Neuro-Degenerative Diseases: An Immunocytochemical Approach

Kun, Alejandra; Rosso, Gonzalo; Canclini, Lucía; Bresque, Mariana; Romeo, Carlos; Cal, Karina; Calliari, Aldo; Hanuz, Alicia; Sotelo‐Silveira, José; Sotelo, Julio

doi:10.5772/35306

Cited by 7 publications

(15 citation statements)

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“…Cytoskeletal homeostasis may be altered in pathological regeneration/degeneration conditions. We have recently communicated that this protein is also present in Schwann cell nuclei; the signals are granular, similar to those described as cytoplasmic aggresomes-like in SC cytoplasm [Kun et al, 2011]. The alteration [also described in a human CMT family by Valentij et al, 1992], is a punctual mutation in pmp22 gene that prevents the normal insertion of PMP-22 protein into myelin .…”

Section: Discussionsupporting

confidence: 59%

“…PMP-22 accumulates in cytoplasmic aggregates with other proteins in lysosomal and endosomal vesicles [Suter and Snipes, 1995a,b]. We have recently communicated that this protein is also present in Schwann cell nuclei; the signals are granular, similar to those described as cytoplasmic aggresomes-like in SC cytoplasm [Kun et al, 2011]. The presence of aggresomes has been found in association with the redistribution of cytoskeletal components.…”

Section: Discussionmentioning

confidence: 85%

“…Recently, we have characterized the molecular expression of actin, tubulin, vimentin, MAG, nucleic acid, ribosomes, and multivesicular bodies in SLI [Kun et al, 2011], and local expression of heavy neurofilament subunit RNA in SLI under normal and pathological conditions (manuscript in redaction). Thus, SLIs seem to be prepared not only for local traffic, but also for communication between Schwann cell domains.…”

Section: Discussionmentioning

confidence: 99%

“…Genotyping was carried out as described in Kun et al [2011]. Briefly, after DNA extraction and PCR amplification using specific primers, the products were digested with Bfal (Fermentas) and the digestion products size were evaluated in a 6% PAGE system.…”

Section: Trembler-j Mice Genotypingmentioning

confidence: 99%

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F‐actin distribution at nodes of Ranvier and Schmidt‐Lanterman incisures in mammalian sciatic nerves

et al. 2012

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Very little is known about the function of the F-actin cytoskeleton in the regeneration and pathology of peripheral nerve fibers. The actin cytoskeleton has been associated with maintenance of tissue structure, transmission of traction and contraction forces, and an involvement in cell motility. Therefore, the state of the actin cytoskeleton strongly influences the mechanical properties of cells and intracellular transport therein. In this work, we analyze the distribution of F-actin at Schmidt-Lanterman Incisures (SLI) and nodes of Ranvier (NR) domains in normal, regenerating and pathologic Trembler J (TrJ/+) sciatic nerve fibers, of rats and mice. F-actin was quantified and it was found increased in TrJ/+, both in SLI and NR. However, SLI and NR of regenerating rat sciatic nerve did not show significant differences in F-actin, as compared with normal nerves. Cytochalasin-D and Latrunculin-A were used to disrupt the F-actin network in normal and regenerating rat sciatic nerve fibers. Both drugs disrupt F-actin, but in different ways. Cytochalasin-D did not disrupt Schwann cell (SC) F-actin at the NR. Latrunculin-A did not disrupt F-actin at the boundary region between SC and axon at the NR domain. We surmise that the rearrangement of F-actin in neurological disorders, as presented here, is an important feature of TrJ/+ pathology as a Charcot-Marie-Tooth (CMT) model.

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Section: Discussionsupporting

confidence: 59%

Section: Discussionmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Section: Trembler-j Mice Genotypingmentioning

confidence: 99%

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F‐actin distribution at nodes of Ranvier and Schmidt‐Lanterman incisures in mammalian sciatic nerves

et al. 2012

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“…Male 70 to 90 days old (P70-P90) wild-type (WT) and heterozygous mice carrying a mutation in pmp-22 (Tr-J) from Jackson Laboratory (strain B6.D2-Pmp22 Tr-J/J) were killed by cervical dislocation. Sciatic nerve dissection was promptly carried out in less than one minute and followed by fixation through immersion in cold freshly prepared 3% w/v paraformaldehyde (PFA) in PHEM buffer (60 mM Pipes, 25 mM Hepes, 10 mM EGTA, 2 mM magnesium chloride, pH 7.2-7.6) for 1 h. This procedure is known to grant a faster fixation than systemic descendent perfusion in the singular case of mice sciatic nerves ( Kun et al, 2012a ; Kun et al, 2012b ). Then, nerves were cryoprotected in sucrose/PHEM at 4 °C (increasing concentrations along 24 h: 5% to 30% w/v) ( Kun et al, 2012a ; Kun et al, 2012b ).…”

Section: Methodsmentioning

confidence: 99%

Poly(ADP-ribosylation) is present in murine sciatic nerve fibers and is altered in a Charcot-Marie-Tooth-1E neurodegenerative model

Lafon-Hughes

Cardeillac

Castillo

et al. 2017

PeerJ

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BackgroundPoly-ADP-ribose (PAR) is a polymer synthesized by poly-ADP-ribose polymerases (PARPs) as a postranslational protein modification and catabolized mainly by poly-ADP-ribose glycohydrolase (PARG). In spite of the existence of cytoplasmic PARPs and PARG, research has been focused on nuclear PARPs and PAR, demonstrating roles in the maintenance of chromatin architecture and the participation in DNA damage responses and transcriptional regulation. We have recently detected non-nuclear PAR structurally and functionally associated to the E-cadherin rich zonula adherens and the actin cytoskeleton of VERO epithelial cells. Myelinating Schwann cells (SC) are stabilized by E-cadherin rich autotypic adherens junctions (AJ). We wondered whether PAR would map to these regions. Besides, we have demonstrated an altered microfilament pattern in peripheral nerves of Trembler-J (Tr-J) model of CMT1-E. We hypothesized that cytoplasmic PAR would accompany such modified F-actin pattern.MethodsWild-type (WT) and Tr-J mice sciatic nerves cryosections were subjected to immunohistofluorescence with anti-PAR antibodies (including antibody validation), F-actin detection with a phalloidin probe and DAPI/DNA counterstaining. Confocal image stacks were subjected to a colocalization highlighter and to semi-quantitative image analysis.ResultsWe have shown for the first time the presence of PAR in sciatic nerves. Cytoplasmic PAR colocalized with F-actin at non-compact myelin regions in WT nerves. Moreover, in Tr-J, cytoplasmic PAR was augmented in close correlation with actin. In addition, nuclear PAR was detected in WT SC and was moderately increased in Tr-J SC.DiscussionThe presence of PAR associated to non-compact myelin regions (which constitute E-cadherin rich autotypic AJ/actin anchorage regions) and the co-alterations experienced by PAR and the actin cytoskeleton in epithelium and nerves, suggest that PAR may be a constitutive component of AJ/actin anchorage regions. Is PAR stabilizing the AJ-actin complexes? This question has strong implications in structural cell biology and cell signaling networks. Moreover, if PAR played a stabilizing role, such stabilization could participate in the physiological control of axonal branching. PARP and PAR alterations exist in several neurodegenerative pathologies including Alzheimer’s, Parkinson’s and Hungtington’s diseases. Conversely, PARP inhibition decreases PAR and promotes neurite outgrowth in cortical neurons in vitro. Coherently, the PARP inhibitor XAV939 improves myelination in vitro, ex vivo and in vivo. Until now such results have been interpreted in terms of nuclear PARP activity. Our results indicate for the first time the presence of PARylation in peripheral nerve fibers, in a healthy environment. Besides, we have evidenced a PARylation increase in Tr-J, suggesting that the involvement of cytoplasmic PARPs and PARylation in normal and neurodegenerative conditions should be re-evaluated.

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Curcumin and Ethanol Effects in Trembler-J Schwann Cell Culture

Alberdi¹,

Rosso²,

Velóz³

et al. 2022

Preprint

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Charcot-Marie-Tooth (CMT) syndrome is the most common progressive human motor and sensory peripheral neuropathy. CMT type 1E is a demyelinating neuropathy affecting Schwann cells due to pmp22 mutations, modelized by Trembler-J mice. Curcumin, a natural polyphenol com-pound obtained from turmeric (Curcuma longa), exhibits dose- and time-varying antitumor, antioxidant and neuroprotective properties, however, the neurotherapeutic actions of curcumin still remain elusive. Here, we propose curcumin as a possible natural treatment capable of enhancing cellular detoxification mechanisms, resulting in an improvement of the neurodegenerative Trembler-J phenotype. Using a refined method for obtaining enriched Schwann cell cultures, we evaluated the neurotherapeutic action of low dose curcumin treatment on the PMP22 expression, and on the chaperones (HSF1 and Hsp27) and autophagy/mTOR (HDAC6 and ribosomes) pathways in Trembler-J and wild-type genotypes. In wild-type Schwann cells, the action of cur-cumin resulted in strong stimulation of the chaperone and macroautophagy pathway, whereas the modulation of ribophagy showed a mild effect. However, despite the promising neuroprotective effects for the treatment of neurological diseases, we report (demonstrate?) that the action of cur-cumin in Trembler-J Schwann cells could be impaired due to the irreversible impact of ethanol used as a common curcumin vehicle necessary for administration. These results contribute to expand our still limited understanding of PMP22 biology in neurobiology, and expose the intrinsic lability of the neurodegenerative Trembler-J genotype. Furthermore, they unravel interesting physiological mechanisms of cellular resilience relevant for to the pharmacological treatment of the neurodegenerative Tremble J phenotype with curcumin and ethanol. We conclude that the analysis of the effects of the vehicle itself is an essential and in-escapable step to comprehensibly assess the own effects and full potential of curcumin treatment for therapeutic purposes.

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The Schwann Cell-Axon Link in Normal Condition or Neuro-Degenerative Diseases: An Immunocytochemical Approach

Cited by 7 publications

References 56 publications

F‐actin distribution at nodes of Ranvier and Schmidt‐Lanterman incisures in mammalian sciatic nerves

F‐actin distribution at nodes of Ranvier and Schmidt‐Lanterman incisures in mammalian sciatic nerves

Poly(ADP-ribosylation) is present in murine sciatic nerve fibers and is altered in a Charcot-Marie-Tooth-1E neurodegenerative model

Curcumin and Ethanol Effects in Trembler-J Schwann Cell Culture

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