Authors: Caruso, Donatella¹; Scurati, Samuele²; Roglio, Ilaria³; Nobbio, Lucilla⁴; Schenone, Angelo⁴; Melcangi, Roberto⁵

Source: Journal of Molecular Neuroscience, Volume 34, Number 3, March 2008 , pp. 249-253(5)

Publisher: Humana Press

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 (PMP22_tg rats; i.e., an experimental model of CMT1A) and of the corresponding wild-type littermates. We observed that, both in PMP22_tg 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 PMP22_tg 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 PMP22_tg rats.

Keywords: Sciatic nerve; GABA-A receptor; Gender; Liquid chromatography tandem mass spectrometry; Peripheral neuropathy

Document Type: Research article

DOI: http://dx.doi.org/10.1007/s12031-007-9029-3

Affiliations: 1: Department of Pharmacological Sciences and Center for Metrological Traceability in Laboratory Medicine, University of Milan, Milan, Italy, 2: Department of Pharmacological Sciences, University of Milan, Milan, Italy, 3: Department of Endocrinology and Center of Excellence on Neurodegenerative Diseases, University of Milan, Via Balzaretti 9, 20133, Milan, Italy, 4: Department of Neuroscience, Ophthalmology and Genetic, and Center of Excellence for Biomedical Research, University of Genoa, Genoa, Italy, 5: Department of Endocrinology and Center of Excellence on Neurodegenerative Diseases, University of Milan, Via Balzaretti 9, 20133, Milan, Italy, Email: roberto.melcangi@unimi.it

Publication date: 2008-03-01

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