Cobalamin (vitamin B12) regulation of PrPC, PrPC-mRNA and copper levels in rat central nervous system

Scalabrino, Giuseppe; Veber, Daniela; Mutti, Elena; Calligaro, Alberto; Milani, Silvano; Tredici, G

doi:10.1016/j.expneurol.2011.11.003

Cited by 11 publications

(34 citation statements)

References 51 publications

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“…We have also demonstrated that EGF increases PrP C -related mRNA synthesis in the SC of Cbl-D rats and, together with Cbl, contributes to maintaining SC and CSF PrP C levels within the normal range (Scalabrino et al, 2012). EGF therefore seems to play a dual role in CNS myelin maintenance (as an effector of Cbl myelinotrophism and as stimulator per se of PrP C synthesis in mammalian CNS).…”

Section: Regulation Of Prp C -Related Mrnasmentioning

confidence: 63%

“…microinjections of Abs with epitopes against various PrP C regions (with the only exception of the Abs with OR region as epitope) invariably die shortly after the beginning of treatment. We observed intramyelinic and interstitial edema in the SC white matter of these rats, without any histological or ultrastructural evidence of neuronal damage or lesions of the heart, lungs, kidneys, and liver (Scalabrino et al, 2012).…”

Section: Gfap and Nf-äb Regulationmentioning

confidence: 64%

“…injections of anti-TNF-␣ Abs, which simultaneously brought about an increase in SC PrP C mRNA levels and the reappearance of a normal SC myelin ultrastructure. SC TNF-␣ levels subsequently normalized and there was no increase in SC and CSF PrP C levels after the partial "spontaneous" repair of SC myelin lesions had been observed (Scalabrino et al, 1997(Scalabrino et al, , 2012.…”

Section: The Cbl and Egf Dyad: Indispensable For Prp C And Myelin Hommentioning

confidence: 96%

“…We have recently demonstrated that Cbl increases PrP C -related mRNA synthesis in SC of Cbl-D rats, and contributes to maintaining the SC and CSF PrP C levels within the normal range (Scalabrino et al, 2012).…”

Section: Regulation Of Prp C -Related Mrnasmentioning

confidence: 99%

“…The increase in PrP C levels was greatly reduced by in vitro pretreatment with proteinase K, thus leading us to suppose that it was mainly due to the whole PrP C molecule in its native form and not to its conformational transformation into the pathological form PrP SC (Scalabrino et al, 2011(Scalabrino et al, , 2012.…”

Section: The Cbl and Egf Dyad: Indispensable For Prp C And Myelin Hommentioning

confidence: 99%

See 4 more Smart Citations

Relationships between cobalamin, epidermal growth factor, and normal prions in the myelin maintenance of central nervous system

Scalabrino

Veber

Tredici

2014

The International Journal of Biochemistry & Cell Biology

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Section: Regulation Of Prp C -Related Mrnasmentioning

confidence: 63%

Section: Gfap and Nf-äb Regulationmentioning

confidence: 64%

Section: The Cbl and Egf Dyad: Indispensable For Prp C And Myelin Hommentioning

confidence: 96%

Section: Regulation Of Prp C -Related Mrnasmentioning

confidence: 99%

Section: The Cbl and Egf Dyad: Indispensable For Prp C And Myelin Hommentioning

confidence: 99%

See 3 more Smart Citations

Relationships between cobalamin, epidermal growth factor, and normal prions in the myelin maintenance of central nervous system

Scalabrino

Veber

Tredici

2014

The International Journal of Biochemistry & Cell Biology

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Myelin damage due to local quantitative abnormalities in normal prion levels: evidence from subacute combined degeneration and multiple sclerosis

Scalabrino

Veber

2013

J Neurol

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Cobalamin (Cbl) deficiency causes an imbalance in some cytokines and growth factors in the central nervous system and peripheral nervous system (PNS) of the rat, and in the serum and cerebrospinal fluid (CSF) of adult Cbl-deficient (Cbl-D) patients. It is conceivable that this imbalance triggers subsequent cellular events. We hypothesized that an imbalance in normal prion (PrP(C)) levels and/or synthesis might be involved in the pathogenesis of Cbl-D neuropathy, and demonstrated that: (1) Cbl deficiency induces excess PrP(C) in rat spinal cord (SC) and PNS, concomitantly with myelin damage and PNS electrophysiological abnormalities; (2) the SC increase is mediated by a local Cbl deficiency-induced excess of tumor necrosis factor-α; (3) myelinotrophic Cbl and epidermal growth factor upregulate PrP(C)-mRNA levels in rat SC; (4) treatment with anti-PrP(C) octapeptide repeat region antibodies normalizes the ultrastructure of the Cbl-D rat SC and PNS myelins, and the PNS electrophysiological abnormalities, without modifying their Cbl-D status; (5) PrP(C) administration to otherwise normal rats causes SC and PNS myelin lesions and PNS electrophysiological abnormalities, similar to those of Cbl-D neuropathy; (6) CSF and serum PrP(C) concentrations in Cbl-D patients are significantly higher than in controls; and (7) these concentrations significantly correlate with their CSF and serum Cbl concentrations. CSF PrP(C) concentrations are significantly lower in patients with multiple sclerosis (MS) than neurological controls, but serum PrP(C) concentrations in patients with non-Cbl-D anemias and CSF PrP(C) concentrations in patients with non-myelin-damaging neurological diseases are normal.

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Epidermal Growth Factor in the CNS: A Beguiling Journey from Integrated Cell Biology to Multiple Sclerosis. An Extensive Translational Overview

Scalabrino

2020

Cell Mol Neurobiol

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This article reviews the wealth of papers dealing with the different effects of epidermal growth factor (EGF) on oligodendrocytes, astrocytes, neurons, and neural stem cells (NSCs). EGF induces the in vitro and in vivo proliferation of NSCs, their migration, and their differentiation towards the neuroglial cell line. It interacts with extracellular matrix components. NSCs are distributed in different CNS areas, serve as a reservoir of multipotent cells, and may be increased during CNS demyelinating diseases. EGF has pleiotropic differentiative and proliferative effects on the main CNS cell types, particularly oligodendrocytes and their precursors, and astrocytes. EGF mediates the in vivo myelinotrophic effect of cobalamin on the CNS, and modulates the synthesis and levels of CNS normal prions (PrPCs), both of which are indispensable for myelinogenesis and myelin maintenance. EGF levels are significantly lower in the cerebrospinal fluid and spinal cord of patients with multiple sclerosis (MS), which probably explains remyelination failure, also because of the EGF marginal role in immunology. When repeatedly administered, EGF protects mouse spinal cord from demyelination in various experimental models of autoimmune encephalomyelitis. It would be worth further investigating the role of EGF in the pathogenesis of MS because of its multifarious effects.

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Cobalamin (vitamin B12) regulation of PrPC, PrPC-mRNA and copper levels in rat central nervous system

Cited by 11 publications

References 51 publications

Relationships between cobalamin, epidermal growth factor, and normal prions in the myelin maintenance of central nervous system

Relationships between cobalamin, epidermal growth factor, and normal prions in the myelin maintenance of central nervous system

Myelin damage due to local quantitative abnormalities in normal prion levels: evidence from subacute combined degeneration and multiple sclerosis

Epidermal Growth Factor in the CNS: A Beguiling Journey from Integrated Cell Biology to Multiple Sclerosis. An Extensive Translational Overview

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