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Neuroactive Steroid Levels in a Transgenic Rat Model of CMT1A Neuropathy

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Abstract

Charcot–Marie–Tooth type 1A (CMT1A) represents 80% of all the demyelinating hereditary motor and sensory neuropathies. As recently suggested, neuroactive steroids may have a role in a therapeutic strategy for peripheral neuropathies, including CMT1A. To this aim, an accurate qualitative and quantitative analysis of neuroactive steroid levels in this disease could be extremely important to define effective pharmacological strategies. We here analyzed by liquid chromatography-tandem mass spectrometry the levels of neuroactive steroids present in the sciatic nerve of male and female peripheral myelin protein 22 transgenic rats (PMP22tg rats; i.e., an experimental model of CMT1A) and of the corresponding wild-type littermates. We observed that, both in PMP22tg rats and in the wild types, the levels of neuroactive steroids, such as progesterone, tetrahydroprogesterone (THP), isopregnanolone (3β,5α-THP), testosterone, dihydrotestosterone, and 5α-androstane-3α, 17β-diol (3α-diol) are sexually dimorphic. It is interesting to note that the levels of 3β,5α-THP and of 3α-diol, which are exclusively detectable in sciatic nerve of female and male rats, respectively, are strongly decreased in PMP22tg rats. 3β,5α-THP and 3α-diol are modulators of gamma-amino butyric acid A receptor. Thus, the present findings may be considered an interesting background for experiments aimed to evaluate the possible therapeutic effects of modulators of this neurotransmitter receptor in male and female PMP22tg rats.

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Acknowledgments

The financial supports of PRIN (2005060584_004), FIRST from University of Milan, Italy, and “Ricerca Finalizzata Ministero della Salute n. 2005/51” to R.C.M. are gratefully acknowledged.

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Authors and Affiliations

  1. Department of Pharmacological Sciences and Center for Metrological Traceability in Laboratory Medicine, University of Milan, Milan, Italy

    Donatella Caruso

  2. Department of Pharmacological Sciences, University of Milan, Milan, Italy

    Samuele Scurati

  3. Department of Endocrinology and Center of Excellence on Neurodegenerative Diseases, University of Milan, Via Balzaretti 9, 20133, Milan, Italy

    Ilaria Roglio & Roberto C Melcangi

  4. Department of Neuroscience, Ophthalmology and Genetic, and Center of Excellence for Biomedical Research, University of Genoa, Genoa, Italy

    Lucilla Nobbio & Angelo Schenone

Authors
  1. Donatella Caruso
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  2. Samuele Scurati
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  3. Ilaria Roglio
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  4. Lucilla Nobbio
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  5. Angelo Schenone
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  6. Roberto C Melcangi
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Correspondence to Roberto C Melcangi.

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Caruso, D., Scurati, S., Roglio, I. et al. Neuroactive Steroid Levels in a Transgenic Rat Model of CMT1A Neuropathy. J Mol Neurosci 34, 249–253 (2008). https://doi.org/10.1007/s12031-007-9029-3

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  • DOI: https://doi.org/10.1007/s12031-007-9029-3

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