The restoration of hippocampal nerve de-myelination by methylcobalamin relates with the enzymatic regulation of homocysteine level in a rat model of moderate grade hepatic encephalopathy
© 2024 Wiley Periodicals LLC..
This article describes how methylcobalamin (MeCbl) restores nerve myelination in a moderate- grade hepatic encephalopathy (MoHE) model of ammonia neurotoxicity. The comparative profiles of myelin basic protein (MBP), homocysteine (Hcy) and methionine synthase (MS: a MeCbl- dependent enzyme) activity versus nerve myelination status were studied in the hippocampus of the control, the MoHE (developed by administering 100 mg/kg bw thioacetamide i.p. for 10 days) and the MoHE rats treated with MeCbl (500 µg/kg BW i.p.) for 7 days. Compared to those of control rats, the hippocampal CA1 and CA3 regions of the MoHE rats showed significantly lower myelinated areas and MBP immunostaining. This coincided with the deranged myelin layering in TEM images, decreased MBP protein and its transcript levels in hippocampus of MoHE rats. However, all these parameters recovered to normal levels after MeCbl treatment. MeCbl is a cofactor of MS that catalyzes the conversion of Hcy to methionine as a feeder step of methylation reactions. We observed significantly increased serum and hippocampal Hcy levels in MoHE rats, however, these levels were restored to control values with a concordant activation of MS due to MeCbl treatment. A significant recovery in neurobehavioral impairments in the MoHE rats due to MeCbl treatment was also observed. These findings suggest that MoHE pathogenesis is associated with deranged nerve myelination in the hippocampus and that MeCbl treatment is able to restore it mainly by activating MS, a MeCbl-dependent Hcy-metabolizing enzyme.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:38 |
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| Enthalten in: |
Journal of biochemical and molecular toxicology - 38(2024), 4 vom: 21. März, Seite e23695 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Roy, Anima [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 22.03.2024 Date Revised 22.03.2024 published: Print Citation Status MEDLINE |
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| doi: |
10.1002/jbt.23695 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 4 | |a The restoration of hippocampal nerve de-myelination by methylcobalamin relates with the enzymatic regulation of homocysteine level in a rat model of moderate grade hepatic encephalopathy |
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| 520 | |a This article describes how methylcobalamin (MeCbl) restores nerve myelination in a moderate- grade hepatic encephalopathy (MoHE) model of ammonia neurotoxicity. The comparative profiles of myelin basic protein (MBP), homocysteine (Hcy) and methionine synthase (MS: a MeCbl- dependent enzyme) activity versus nerve myelination status were studied in the hippocampus of the control, the MoHE (developed by administering 100 mg/kg bw thioacetamide i.p. for 10 days) and the MoHE rats treated with MeCbl (500 µg/kg BW i.p.) for 7 days. Compared to those of control rats, the hippocampal CA1 and CA3 regions of the MoHE rats showed significantly lower myelinated areas and MBP immunostaining. This coincided with the deranged myelin layering in TEM images, decreased MBP protein and its transcript levels in hippocampus of MoHE rats. However, all these parameters recovered to normal levels after MeCbl treatment. MeCbl is a cofactor of MS that catalyzes the conversion of Hcy to methionine as a feeder step of methylation reactions. We observed significantly increased serum and hippocampal Hcy levels in MoHE rats, however, these levels were restored to control values with a concordant activation of MS due to MeCbl treatment. A significant recovery in neurobehavioral impairments in the MoHE rats due to MeCbl treatment was also observed. These findings suggest that MoHE pathogenesis is associated with deranged nerve myelination in the hippocampus and that MeCbl treatment is able to restore it mainly by activating MS, a MeCbl-dependent Hcy-metabolizing enzyme | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Hepatic encephalopathy (HE) | |
| 650 | 4 | |a Homocysteine (Hcy) | |
| 650 | 4 | |a Methionine synthase (MS) | |
| 650 | 4 | |a Methylcobalamin (MeCbl) | |
| 650 | 4 | |a Myelin basic protein (MBP) | |
| 650 | 7 | |a mecobalamin |2 NLM | |
| 650 | 7 | |a BR1SN1JS2W |2 NLM | |
| 650 | 7 | |a Vitamin B 12 |2 NLM | |
| 650 | 7 | |a P6YC3EG204 |2 NLM | |
| 650 | 7 | |a Methionine |2 NLM | |
| 650 | 7 | |a AE28F7PNPL |2 NLM | |
| 700 | 1 | |a Trigun, Surendra Kumar |e verfasserin |4 aut | |
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