Progesterone and its derivatives dihydroprogesterone and tetrahydroprogesterone reduce myelin fiber morphological abnormalities and myelin fiber loss in the sciatic nerve of aged rats

Azcoitia, Íñigo; Leonelli, Emanuela; Magnaghi, Valerio; Veiga, Sergio; Garcia-Segura, Luis Miguel; Melcangi, Roberto Cosimo

doi:10.1016/s0197-4580(02)00234-8

Cited by 146 publications

(128 citation statements)

References 56 publications

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“…In line with study Azcoitia et al (2003) and Yorek et al (2002) study, our study showed that STZ administration increases morphological changes of myelin layer (sheath) in sciatic nerve. MFD and AD in diabetic groups of sham and DMSO showed significant decrease compared to the control group, while melatonin prevented morphological changes of sciatic nerve in diabetic rats.…”

Section: Discussionsupporting

confidence: 90%

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Effects of Melatonin in Prevention of Neuropathy in STZ-Induced Diabetic Rats

Zangiabadi¹,

Sheibani²,

Asadi-Shekaari³

et al. 2011

American Journal of Pharmacology and Toxicology

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Problem statement: Diabetes mellitus occurs mainly with chronic polyneuropathy, and oxidative stress plays an important role in emergence of most neurologic and behavioral changes in diabetic patients. Many studies have focused on the beneficial effects of various antioxidants such as melatonin on diabetic neuropathy. The aim of this study is to evaluate the effect of melatonin in prevention of neuropathy in Streptozotocin-induced diabetic rats. After prescribing Streptozotocin (STZ), treatment rats received melatonin (10 mg kg day −1 ) or DMSO for a period of 6 weeks. Approach: At the end of the sixth week, non diabetic control group, diabetic control group (sham) and treated rats were examined by thermal pain response tests (hot plate and tail flick). The horizontal and vertical activities of rats were measured in an open field test. After that, Motor Nerve Conduction Velocity (MNCV) of sciatic-tibial nerve recorded. Also, to study morphological alterations resulting from diabetic neuropathy of sciatic nerve, Myelinated Fiber Diameter (MFD), Axon Diameter (AD) and Myelin Sheath Diameter (MSD) were evaluated by light microscope. Results: According to hot plate results, response time to thermal pain at the end of sixth week in sham group showed a significant decrease in comparison with the control group (p<0.01). In hot plate test, although melatonin approximated to the response time to control group, the significant difference was not observed among melatonin receivers and other groups. In the open field test, Total Distance Moved (TDM) and mobility duration showed significant decrease in sham and DMSO groups in comparison to the control and melatonin groups. Diabetic rats treated with melatonin showed significant increase in MNCV compared to sham and DMSO groups (p<0.05). In morphological study, pretreatment with Melatonin significantly reversed sciatic nerve diameters (MFD, AD, and MSD) reduction in diabetic rats. Electron microscopy showed myelin splitting and myelin sheath infolding in diabetic control group compare to non diabetic group. Conclusion: This study showed that melatonin can decrease the destructive progress of diabetes and causes neuroprotection against damages resulting from STZinduced hyperglycemia.

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Section: Discussionsupporting

confidence: 90%

“…MNCV decrease can be resulted from the change of nerve fiber diameter or myelin layer defect (Yorek et al, 2002;Azcoitia et al, 2003). In line with study Azcoitia et al (2003) and Yorek et al (2002) study, our study showed that STZ administration increases morphological changes of myelin layer (sheath) in sciatic nerve.…”

Section: Discussionsupporting

confidence: 87%

Effects of Melatonin in Prevention of Neuropathy in STZ-Induced Diabetic Rats

Zangiabadi¹,

Sheibani²,

Asadi-Shekaari³

et al. 2011

American Journal of Pharmacology and Toxicology

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“…Neuroactive steroids, using multiple signaling mechanisms may influence many physiological parameters of rat peripheral nerves, such as synthesis of myelin proteins and of myelin membranes, Schwann cell proliferation and function of the axonal compartments. Alterations of these parameters are clearly evident in peripheral neuropathy, such as that occurring after peripheral nerve injury, during aging or in hereditary demyelinating diseases [2][3][4]. In the experimental models of peripheral neuropathy so far taken into consideration, neuroactive steroids exert important neuroprotective effects, and consequently could be considered as a therapeutic approach to counteract neurodegeneration.…”

mentioning

confidence: 99%

“…Neuroactive steroids are also able to counteract degenerative effects of aging in peripheral nerves [2,6]. That is very important because the aging process induces important biochemical and morphological changes in peripheral nerves.…”

mentioning

confidence: 99%

“…That is very important because the aging process induces important biochemical and morphological changes in peripheral nerves. For instance, aging is associated with a decrease in the synthesis of P0 and PMP22, large myelinated fibers undergo atrophy, while myelin sheaths increase in thickness and show various irregularities, such as myelin ballooning, splitting, infolding, reduplication and remyelination [2,6]. A reduction in the number of density myelinated fibers has been reported with aging in peripheral nerves of several animal species and this effect is particularly evident in myelinated fibers of small caliber.…”

mentioning

confidence: 99%

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Therapeutic approaches to peripheral neuropathy based on neuroactive steroids

Melcangi

Garcia-Segura

2006

Expert Review of Neurotherapeutics

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Neuroactive Steroids and Peripheral Neuropathy

Melcangi

Giatti

Pesaresi

et al. 2011

Hormones in Neurodegeneration, Neuroprotection, and Neurogenesis

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Peripheral neuropathy, either inherited or acquired, is a very common disorder for which effective clinical treatments are not yet available. Neuroactive steroids such as progesterone, testosterone, and their reduced metabolites represent a promising therapeutic option for peripheral neuropathy. Peripheral nerves are able to synthesize and metabolize neuroactive steroids and are a target for these molecules since they express classical and nonclassical steroid receptors. Neuroactive steroids modulate the expression of key transcription factors (TFs) for Schwann cell function, regulate Schwann cell proliferation, and promote the expression of myelin proteins. Interestingly, they are also able to counteract biochemical, morphological, and functional alterations of peripheral nerves in different experimental models of neuropathy, including the alterations caused by aging, diabetic neuropathy, and physical injury. Therefore, neuroactive steroids and pharmacological agents that are able to increase their local synthesis and the synthetic ligands for their receptors offer a promising potential for the treatment of different forms of peripheral neuropathy.

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Progesterone and its derivatives dihydroprogesterone and tetrahydroprogesterone reduce myelin fiber morphological abnormalities and myelin fiber loss in the sciatic nerve of aged rats

Cited by 146 publications

References 56 publications

Effects of Melatonin in Prevention of Neuropathy in STZ-Induced Diabetic Rats

Effects of Melatonin in Prevention of Neuropathy in STZ-Induced Diabetic Rats

Therapeutic approaches to peripheral neuropathy based on neuroactive steroids

Neuroactive Steroids and Peripheral Neuropathy

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