Neuroactive steroids prevent peripheral myelin alterations induced by diabetes

Veiga, Sergio; Leonelli, Emanuela; Beelke, Manolo; Garcia-Segura, Luis Miguel; Melcangi, Roberto Cosimo

doi:10.1016/j.neulet.2006.03.058

Cited by 54 publications

(33 citation statements)

References 26 publications

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“…Moreover, the axon degeneration is relation with pathogenesis of negative signs of DPN (Thomas, 1999). As reported before (Veiga et al, 2006), the most abundant nerve abnormality observed in our study was that both myelinated fiber and extramedullary fiber of the sciatic nerve were markedly decreased in diabetic rats, as opposed to the control group.…”

Section: Discussionsupporting

confidence: 78%

Protective effect of mulberry flavonoids on sciatic nerve in alloxan-induced diabetic rats

Dong-lian

Deng

et al. 2014

Braz. J. Pharm. Sci.

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Mulberry leaves (Morus alba L.) are a traditional Chinese medicine for blood serum glucose reduction. This study evaluated the protective effects of mulberry flavonoids on sciatic nerve in alloxan-induced diabetic rats. In this study, 80 Sprague-Dawley rats were divided into five groups: A (control), B (diabetic treated with saline), C-D (diabetic treated with 0.3, 0.1 g/kg mulberry flavonoids once a day for 8 weeks) and E (diabetic treated with 0.3 mg/kg methycobal). The diabetic condition was induced by intraperitoneal injection of 200 mg/kg alloxan dissolved in saline. At the end of the experimental period, blood, and tissue samples were obtained for biochemical and histopathological investigation. Treatment with 0.3 g/kg mulberry flavonoids significantly inhibited the elevated serum glucose (P< 0.01). The increased myelin sheath area (P< 0.01), myelinated fiber cross-sectional area and extramedullary fiber number (P< 0.05) were also reduced in alloxan-induced rats treated with 0.3 g/kg mulberry flavonoids. 0.3 g/kg mulberry flavonoids also markedly decreased onion-bulb type myelin destruction and degenerative changes of mitochondria and Schwann cells. These findings demonstrate that mulberry flavonoids may improve the recovery of a severe peripheral nerve injury in alloxan-induced diabetic rats and is likely to be useful as a potential treatment on peripheral neuropathy (PN) in diabetic rats. Uniterms:Morus alba L./pharmacognosy. Mulberry flavonoids/protective effects/experimental study. Diabetic neuropathy/experimental study. Medicinal plants. Diabetics/treatment/experimental study.Folhas de amoreira (Morus alba L.) é um medicamento tradicional chinês para a redução da glicose no soro sanguíneo. Avaliaram-se, neste trabalho, os efeitos protetores dos flavonóides de amora no nervo ciático em ratos diabéticos aloxano-induzidos. Dividiram-se 80 ratos Sprague-Dawley em cinco grupos: A (controle), B (diabétidos tratados com solução salina), C-D (diabéticos tratados com 0,3, 0,1 g/kg) e E (diabéticos tratados com 0,3 mg de metilcobal).A diabetes foi induzida por injeção intraperitoneal de 200 mg/kg de aloxana dissolvida em solução salina. No final do período experimental, obtiveramse amostras de sangue e de tecido para investigação bioquímica e histopatológica. O tratamento com 0,3 g/kg de flavonóides da amoreira inibiu, significativamente, a elevação de glicose no soro (p <0,01). O aumento da área da bainha de mielina (p <0,01), da área de fibra da seção transversal e do número de fibras mielinizadas extramedulares (p <0,05) foi também reduzido em ratos aloxânicos, tratados com 0,3 g/kg flavonóides de amora. Flavonóides da amoreira na dose de 0,3 g/kg também diminuiram, acentuadamente, a destruição da mielina do tipo bulbo de cebola e as alterações degenerativas das células mitocôndrias e das células de Schwann. Estes resultados demonstram que os flavonóides da amoreira podem melhorar a recuperação de uma lesão nervosa periférica grave em ratos com diabetes, induzida por aloxana, e parece ser útil como tratament...

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Section: Discussionsupporting

confidence: 78%

Protective effect of mulberry flavonoids on sciatic nerve in alloxan-induced diabetic rats

Dong-lian

Deng

et al. 2014

Braz. J. Pharm. Sci.

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“…The most abundant myelin abnormality, as in the case of aging rats, is the presence of myelin infoldings in the axoplasm. P and DHP are able to counteract the increase in the number of fibers with myelin infoldings induced by STZ treatment in the sciatic nerve [13]. This effect is very similar to that mentioned above on the morphological alterations of myelin in the sciatic nerve of aged rats [2,6].…”

supporting

confidence: 79%

“…Recent evidence suggests that P and DHP may prevent myelin structural abnormalities induced by experimental diabetes in rats [13]. Peripheral neuropathy is the most frequent symptomatic complication of diabetes mellitus and potentially one of the most devastating.…”

mentioning

confidence: 99%

Therapeutic approaches to peripheral neuropathy based on neuroactive steroids

Melcangi

Garcia-Segura

2006

Expert Review of Neurotherapeutics

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“…These alterations include myelin invaginations in the axoplasm (infoldings) and myelin evaginations in the Schwann cell cytoplasm (outfoldings), as well as alterations in myelin compaction such as abnormally wide incisures and aberrant separation of myelin lamellae. Similar to those seen in aged rodents ( 44 ), the predominant myelin abnormalities found in STZ-treated rats are myelin infoldings ( 13 ).…”

Section: Discussionmentioning

confidence: 57%

“…Both LXR ␣ and LXR ␤ (NR1H3 and NR1H2) are expressed in sciatic nerve ( 24 ). Neuroactive steroid levels are decreased in peripheral nerves of STZ diabetic rats ( 25,26 ), and treatments that restore their levels improve DPN and myelin function ( 13,27,28 acquisition of MS/MS spectra. Changes between detected phospholipid families were calculated as percent of single phospholipid species normalized to total phospholipid analyzed.…”

Section: Myelin Lipidomic Analysesmentioning

confidence: 99%

Diabetes-induced myelin abnormalities are associated with an altered lipid pattern: protective effects of LXR activation

Cermenati

Abbiati

Cermenati

et al. 2012

Journal of Lipid Research

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Diabetic peripheral neuropathy (DPN) appears frequently in patients diagnosed with type 1 or type 2 diabetes ( 1-3 ). The extent of abnormalities is more pronounced if the hyperglycemia is not controlled properly ( 4, 5 ). DPN is associated with deleterious changes in peripheral nerves, such as myelin damage and decrease in nerve conduction velocity ( 4-9 ). Similar structural abnormalities and neurophysiological changes have been observed in the peripheral nerves of streptozotocin (STZ)-treated rats, an experimental model that captures many features of type 1 diabetes ( 10-12 ). As it is seen in diabetic subjects, STZtreated rats show increased morphological alterations in the myelinated fi bers of the sciatic nerve ( 13 ).Abstract Diabetic peripheral neuropathy (DPN) is characterized by myelin abnormalities; however, the molecular mechanisms underlying such defi cits remain obscure. To uncover the effects of diabetes on myelin alterations, we have analyzed myelin composition. In a streptozotocintreated rat model of diabetic neuropathy, analysis of sciatic nerve myelin lipids revealed that diabetes alters myelin's phospholipid, FA, and cholesterol content in a pattern that can modify membrane fl uidity. Reduced expression of relevant genes in the FA biosynthetic pathway and decreased levels of the transcriptionally active form of the lipogenic factor sterol-regulatory element binding factor-1c (SREBF-1c) were found in diabetic sciatic nerve. Expression of myelin's major protein, myelin protein zero (P0), was also suppressed by diabetes. In addition, we confi rmed that diabetes induces sciatic nerve myelin abnormalities, primarily infoldings that have previously been associated with altered membrane fl uidity. In a diabetic setting, synthetic activator of the nuclear receptor liver X receptor (LXR) increased SREBF-1c function and restored myelin lipid species and P0 expression levels to normal. These LXR-modulated improvements were associated with restored myelin structure in sciatic nerve and enhanced performance in functional tests such as thermal nociceptive threshold and nerve conduction velocity. These fi ndings demonstrate an important role for the LXR-SREBF-1c axis in protection from diabetes-induced myelin abnormalities .-

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Neuroactive steroids prevent peripheral myelin alterations induced by diabetes

Cited by 54 publications

References 26 publications

Protective effect of mulberry flavonoids on sciatic nerve in alloxan-induced diabetic rats

Protective effect of mulberry flavonoids on sciatic nerve in alloxan-induced diabetic rats

Therapeutic approaches to peripheral neuropathy based on neuroactive steroids

Diabetes-induced myelin abnormalities are associated with an altered lipid pattern: protective effects of LXR activation

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