Testosterone derivatives are neuroprotective agents in experimental diabetic neuropathy

Roglio, Ilaria; Bianchi, Roberto; Giatti, Silvia; Cavaletti, Guido; Caruso, Donatella; Scurati, Silvia; Crippa, Donatella; García‐Segura, Luis M.; Camozzi, Francesca; Lauria, Giuseppe; Melcangi, Roberto Cosimo

doi:10.1007/s00018-007-7002-5

Cited by 61 publications

(47 citation statements)

References 70 publications

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“…More recent studies have been unable to confirm this apparent increase in epidermal and dermal innervation in diabetic rodents and instead have shown a reduction in epidermal innervation in rat models of diabetic neuropathy (Bianchi et al, 2004;Lauria et al, 2005;Toth et al 2006;Leonelli et al, 2007;Roglio et al, 2007, Obrosova et al, 2007, which accompanies other nerve disorders and mirrors the reduction observed in human subjects with longer durations of diabetes. Together, these data suggest that rats may be useful for modeling loss of cutaneous innervation in diabetic neuropathy and for investigating the underlying pathophysiolgic mechanisms.…”

Section: Animal Modelsmentioning

confidence: 90%

“…In a more recent study, treatment with a poly(ADP-ribose) polymerase (PARP) inhibitor prevented reductions in IENF density and partially alleviated thermal hypoalgesia in STZ-diabetic rats (Obrosova et al, 2007). There is also evidence that steroid hormones or their metabolites may have protective effects against cutaneous nerve fiber loss (Leonelli et al, 2007;Roglio et al, 2007). In the STZ model, treatment with progesterone, dihydroprogesterone or tetrahydroprogesterone was able to prevent a reduction in IENF density and reverse established thermal hypoalgesia (Leonelli et al, 2007).…”

Section: Therapeutic Interventionsmentioning

confidence: 99%

“…However, whether or not IENF loss is affected by the presence or absence of insulin is an important question. While several studies have reported a reduction in IENF density in rat models of type 1 diabetes (Bianchi et al, 2004;Lauria et al, 2005;Leonelli et al, 2007;Roglio et al, 2007), the effects of hyperglycemia on epidermal innervation in rat models of type 2 diabetes remain unexplored. Fiber loss has been reported in mouse models of type 2 diabetes (Gibran et al, 2002;Drel et al, 2006;Vareniuk et al, 2007), although these models can show insulinopenia in later stages of the disease.…”

Section: Pathogenic Mechanismsmentioning

confidence: 99%

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Epidermal nerve fiber quantification in the assessment of diabetic neuropathy

2008

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SummaryAssessment of cutaneous innervation in skin biopsies is emerging as a valuable means of both diagnosing and staging diabetic neuropathy. Immunolabeling, using antibodies to neuronal proteins such as protein gene product 9.5, allows for the visualization and quantification of intraepidermal nerve fibers. Multiple studies have shown reductions in intraepidermal nerve fiber density in skin biopsies from patients with both type 1 and type 2 diabetes. More recent studies have focused on correlating these changes with other measures of diabetic neuropathy. A loss of epidermal innervation similar to that observed in diabetic patients has been observed in rodent models of both type 1 and type 2 diabetes and several therapeutics have been reported to prevent reductions in intraepidermal nerve fiber density in these models. This review discusses the current literature describing diabetesinduced changes in cutaneous innervation in both human and animal models of diabetic neuropathy.

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Section: Animal Modelsmentioning

confidence: 90%

Section: Therapeutic Interventionsmentioning

confidence: 99%

Section: Pathogenic Mechanismsmentioning

confidence: 99%

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Epidermal nerve fiber quantification in the assessment of diabetic neuropathy

2008

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“…36 A decrease of DHT levels and 5-α-reductase expression occurs in the sciatic nerve in experimental models of diabetes. 37 If diabetic status itself produced a strong impairment of SRD5A1 function, the small difference in expression or function of this enzyme due to genetic polymorphisms would be irrelevant in its presence. This hypothesis would explain the trend towards a modification of the association between SRD5A1 polymorphism and PAD by diabetic status, observed in the present study.…”

Section: Discussionmentioning

confidence: 99%

ICAM-1 and SRD5A1 gene polymorphisms in symptomatic peripheral artery disease

et al. 2014

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The genotype distribution of two gene polymorphisms, previously associated with peripheral artery disease (PAD), has been evaluated in a population of diabetic (DPAD) and non-diabetic (NDPAD) patients affected by symptomatic PAD (stages II-IV). A decreased frequency of the AA genotype of rs5498 (ICAM-1) was observed in the PAD subjects compared to controls but this result did not reach statistical significance (p=0.06 by chi-squared test). On the contrary, a significant increase in the frequency of the GG homozygous genotype of rs248793 (SRD5A1) was observed in the PAD patient group in comparison to controls (p=0.01). These data confirm that the GG genotype of rs248793 in the SRD5A1 gene is significantly associated with symptomatic PAD and show a trend towards a stronger association with the non-diabetic status.

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“…Moreover, chronic steroid treatment with P (or with its derivatives), DHP, and THP counteracted the impairment of NCV and thermal threshold, restoring skin innervation density and P0 and PMP22 mRNA levels, and improving Na + , K + -ATPase activity [92]. In addition, T and its derivatives including DHT and 3α-diol can reverse behavioral, neurophysiological, morphological, and biochemical alterations induced by peripheral diabetic neuropathy [93].…”

Section: Diabetic Neuropathymentioning

confidence: 99%

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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Testosterone derivatives are neuroprotective agents in experimental diabetic neuropathy

Cited by 61 publications

References 70 publications

Epidermal nerve fiber quantification in the assessment of diabetic neuropathy

Epidermal nerve fiber quantification in the assessment of diabetic neuropathy

ICAM-1 and SRD5A1 gene polymorphisms in symptomatic peripheral artery disease

Neuroactive Steroids and Peripheral Neuropathy

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