Neurosteroids: Trophic and behavioral effects

• Research unit: EU RFP
• Project number: 96.0290

Key words (English)

Neurosteroids; myelin; gene regulation

Alternative project number (English)

EU project number: BMH4CT972359

Research programs (English)

EU-programme: 4. Frame Research Programme - 4.2 Agriculture and agroindustry

Short description (English)

See abstract

Partners and International Organizations (English)

Coordinator: INSERM U33,
Bicêtre (F)

Abstract (English)

The nervous system can synthesize and metabolize steroids which are called 'neurosteroids'. The aim of this collaborative project is to examine the merit of this concept and to explore the therapeutic value of neurosteroids in the treatment of lesions and diseases of the nervous system. Since Schwann cells and oligodendrocytes synthesize the neurosteroid pregnenolone from cholesterol, we have examined the effects of neurosteroids on genes crucially involved in myelin formation. This work was based on previous observations that progesterone strongly promotes myelination in the PNS. In the first part of this project, we demonstrated that this regulation is, at least in part, mediated by the specific activation of the promoters of the myelin genes P0 and PMP22. In the second part, we have shown that peripheral-type benzodiazepine receptor (PBR) ligands represent a tantalizing possibility to increase steroid levels in peripheral nerves and, possibly, ameliorate myelination in injury and disease. We are currently testing this hypothesis by examining the effects of PBR ligands in transgenic mouse models of hereditary neuropathies.

References in databases (English)

Swiss Database: Euro-DB of the
State Secretariat for Education and Research
Hallwylstrasse 4
CH-3003 Berne, Switzerland
Tel. [phone]
Swiss Project-Number: 96.0290