Perineurial cells filled with collagen in ‘atypical’ Cogan’s syndrome

Nolte, Kay; Hans, Volkmar J.; C, Schattenfroh; Weis, Joachim; Schröder, Johann Michael

doi:10.1007/s00401-007-0290-x

Cited by 9 publications

(4 citation statements)

References 21 publications

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“…This hypothesis is consistent with the growing literature that perineurial cells are crucial for developing, as well as recently regenerating, peripheral nerves (Kucenas, Takada et al 2008; Binari, Lewis et al 2013). Perineurial cells may also be important in peripheral neuropathies since they become inflamed and reduce their expression of connexins in diabetic rats (Pitre, Seifert et al 2001), as well as develop pathologic changes in human neuropathies (Johnson, Brendel et al 1981; King, Llewelyn et al 1988; Hill and Williams 2004; Nolte, Hans et al 2008). Our results provide, for the first time, a potential mechanism for this supportive role in developing and regenerating axons—namely, providing metabolic energy substrates, in the form of lactate, to Schwann cells and axons.…”

Section: Resultsmentioning

confidence: 99%

Deficiency in monocarboxylate transporter 1 (MCT1) in mice delays regeneration of peripheral nerves following sciatic nerve crush

Morrison

Tsingalia

Vidensky

et al. 2015

Experimental Neurology

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Peripheral nerve regeneration following injury occurs spontaneously, but many of the processes require metabolic energy. The mechanism of energy supply to axons has not previously been determined. In the central nervous system, monocarboxylate transporter 1 (MCT1), expressed in oligodendroglia, is critical for supplying lactate or other energy metabolites to axons. In the current study, MCT1 is shown to localize within the peripheral nervous system to perineurial cells, dorsal root ganglion neurons, and Schwann cells by MCT1 immunofluorescence and MCT1 tdTomato BAC reporter mice. To investigate whether MCT1 is necessary for peripheral nerve regeneration, sciatic nerves in MCT1 heterozygous null mice are crushed and peripheral nerve regeneration quantified electrophysiologically and anatomically. Compound muscle action potential (CMAP) recovery is delayed from a median of 21 days in wild-type mice to greater than 38 days in MCT1 heterozygote null mice. In fact, half of the MCT1 heterozygote null mice have no recovery of CMAP at 42 days, while all of the wild-type mice recovered. In addition, muscle fibers remain 40% more atrophic and neuromuscular junctions 40% more denervated at 42 days post-crush in the MCT1 heterozygote null mice than wild-type mice. The delay in nerve regeneration is not only in motor axons, as the number of regenerated axons in the sural sensory nerve of MCT1 heterozygote null mice at 4 weeks and tibial mixed sensory and motor nerve at 3 weeks is also significantly reduced compared to wild-type mice. This delay in regeneration may be partly through failed Schwann cell function, as there is reduced early phagocytosis of myelin debris and remyelination of axon segments. These data for the first time demonstrate that MCT1 is critical for regeneration of both sensory and motor axons in mice following sciatic nerve crush.

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Section: Resultsmentioning

confidence: 99%

Deficiency in monocarboxylate transporter 1 (MCT1) in mice delays regeneration of peripheral nerves following sciatic nerve crush

Morrison

Tsingalia

Vidensky

et al. 2015

Experimental Neurology

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“…Neuropathology. Resin embedding of the glutaraldehyde-fixed sural nerve biopsy tissue and subsequent electron microscopy was performed using standard procedures (34).…”

Section: Methodsmentioning

confidence: 99%

DEGS1-associated aberrant sphingolipid metabolism impairs nervous system function in humans

Karsai

Kraft

Haag

et al. 2019

Journal of Clinical Investigation

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102

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Volume 129 Number 3 March 2019 conjugation of L-serine and palmitoyl-CoA, the rate-limiting step catalyzed by serine palmitoyltransferase (SPT). The immediate product 3-keto-sphinganine is reduced to sphinganine (SA), which is then N-acylated to dihydroceramide (dhCer) by 1 of 6 ceramide synthase isoforms (CerS1-6) (4). In the final step, dhCer is converted to ceramide by the insertion of a Δ4,5 trans (Δ4E) double bond into the SA backbone. This final conversion is catalyzed by the Δ4-dihydroceramide desaturase DEGS1 (5). On the catabolic side, ceramides are deacylated by ceramidases to form sphingosine (SO), which can be either recycled back to ceramides (sal-BACKGROUND. Sphingolipids are important components of cellular membranes and functionally associated with fundamental processes such as cell differentiation, neuronal signaling, and myelin sheath formation. Defects in the synthesis or degradation of sphingolipids leads to various neurological pathologies; however, the entire spectrum of sphingolipid metabolism disorders remains elusive. METHODS.A combined approach of genomics and lipidomics was applied to identify and characterize a human sphingolipid metabolism disorder. RESULTS.By whole-exome sequencing in a patient with a multisystem neurological disorder of both the central and peripheral nervous systems, we identified a homozygous p.Ala280Val variant in DEGS1, which catalyzes the last step in the ceramide synthesis pathway. The blood sphingolipid profile in the patient showed a significant increase in dihydro sphingolipid species that was further recapitulated in patient-derived fibroblasts, in CRISPR/Cas9-derived DEGS1-knockout cells, and by pharmacological inhibition of DEGS1. The enzymatic activity in patient fibroblasts was reduced by 80% compared with wild-type cells, which was in line with a reduced expression of mutant DEGS1 protein. Moreover, an atypical and potentially neurotoxic sphingosine isomer was identified in patient plasma and in cells expressing mutant DEGS1. CONCLUSION.We report DEGS1 dysfunction as the cause of a sphingolipid disorder with hypomyelination and degeneration of both the central and peripheral nervous systems.(OMIM #617575) (19-21), but also with axonal peripheral neuropathy without renal or adrenal deficiencies (22).Here, we identify DEGS1 dysfunction as the cause of an SL disorder with leukodystrophy and hypomyelination of the peripheral nervous system.

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“…In such cases, perineurial cells often arranged themselves into pseudo-onion bulb-like whorls around Schwann cells and axons in varying stages of degeneration [ 51 ]. Furthermore, collagen-containing cells have been identified as perineurial cells in a case of atypical Cogan’s syndrome, sometimes associated with endoneurial blood vessels connected to the surrounding perineurium by perineurial septae [ 52 ]. Electron microscopy of the tightly packed cells, which formed the reactive septae within damaged spinal nerve roots, and of the thickened perineurium surrounding these nerve roots in the present study revealed a uniform morphology, with cell nuclei containing medium-dense euchromatin surrounded by a rim of heterochromatin, abundant, tight junctions between numerous thin, overlapping cell processes, multiple pinocytotic vesicles, and a discontinuous basal lamina, representing some of the typical ultrastructural characteristics of perineurial cells [ 53 , 54 , 55 , 56 , 57 ].…”

Section: Discussionmentioning

confidence: 99%

Characterization of a Novel Aspect of Tissue Scarring Following Experimental Spinal Cord Injury and the Implantation of Bioengineered Type-I Collagen Scaffolds in the Adult Rat: Involvement of Perineurial-like Cells?

Altinova

Achenbach

Palm

et al. 2022

IJMS

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Numerous intervention strategies have been developed to promote functional tissue repair following experimental spinal cord injury (SCI), including the bridging of lesion-induced cystic cavities with bioengineered scaffolds. Integration between such implanted scaffolds and the lesioned host spinal cord is critical for supporting regenerative growth, but only moderate-to-low degrees of success have been reported. Light and electron microscopy were employed to better characterise the fibroadhesive scarring process taking place after implantation of a longitudinally microstructured type-I collagen scaffold into unilateral mid-cervical resection injuries of the adult rat spinal cord. At long survival times (10 weeks post-surgery), sheets of tightly packed cells (of uniform morphology) could be seen lining the inner surface of the repaired dura mater of lesion-only control animals, as well as forming a barrier along the implant–host interface of the scaffold-implanted animals. The highly uniform ultrastructural features of these scarring cells and their anatomical continuity with the local, reactive spinal nerve roots strongly suggest their identity to be perineurial-like cells. This novel aspect of the cellular composition of reactive spinal cord tissue highlights the increasingly complex nature of fibroadhesive scarring involved in traumatic injury, and particularly in response to the implantation of bioengineered collagen scaffolds.

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Perineurial cells filled with collagen in ‘atypical’ Cogan’s syndrome

Cited by 9 publications

References 21 publications

Deficiency in monocarboxylate transporter 1 (MCT1) in mice delays regeneration of peripheral nerves following sciatic nerve crush

Deficiency in monocarboxylate transporter 1 (MCT1) in mice delays regeneration of peripheral nerves following sciatic nerve crush

DEGS1-associated aberrant sphingolipid metabolism impairs nervous system function in humans

Characterization of a Novel Aspect of Tissue Scarring Following Experimental Spinal Cord Injury and the Implantation of Bioengineered Type-I Collagen Scaffolds in the Adult Rat: Involvement of Perineurial-like Cells?

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