CMT 1A: Neuroactive Steroid Levels in a Transgenic Rat Model Neuropathy

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J Mol Neurosci. 2008 Jan 9

Neuroactive Steroid Levels in a Transgenic Rat Model of CMT1A

Neuropathy.

Caruso D, Scurati S, Roglio I, Nobbio L, Schenone A, Melcangi RC.

Department of Pharmacological Sciences and Center for Metrological

Traceability in Laboratory Medicine, University of Milan, Milan,

Italy.

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 (3beta,5alpha-THP),

testosterone, dihydrotestosterone, and 5alpha-androstane-3alpha,

17beta-diol (3alpha-diol) are sexually dimorphic.

It is interesting to note that the levels of 3beta,5alpha-THP and of

3alpha-diol, which are exclusively detectable in sciatic nerve of

female and male rats, respectively, are strongly decreased in PMP22

(tg) rats. 3beta,5alpha-THP and 3alpha-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.