Forschungs- & Entwicklungsinformationsdienst der Gemeinschaft - CORDIS

Neurosteroid analysis by GC/MS

To better understand the pathophysiological significance of neurosteroids, it was necessary to develop a new method for the accurate measure of their low levels within small samples of nervous tissue. With the support of the European Community (Biomed 2 contract BMH4972359), partner 1 has developed a very sensitive micro-assay, allowing to accurately measuring low steroid levels in small tissue samples by gas chromatography/mass spectrometry (GC/MS) ( His laboratory thus became a "Centralized European Facility" for the measure of neurosteroids.

Within the frame of the present project, reference values for steroid levels in rat, mouse and human nervous tissues and plasma have been provided by gas chromatography/mass spectrometry (GC/MS). The concentrations of steroids measured by GC/MS technology not always correspond to the ones previously determined by less accurate assay procedures such as radioimmunoassays.

The "brain cartography" of neurosteroids has been established for the rat and mouse and the neuroanatomical distribution and developmental changes in the expression of the 3b-hydroxysteroid dehydrogenase, enzyme, which converts pregnenolone to progesterone, has been described. Neurosteroid levels were found to change with age and in response to injury.

Large amounts of lipoidic derivatives of pregnenolone and dehydroepiandrosterone have been identified in rat and human brain tissue and plasma. This finding may have important consequences for our understanding of neurosteroid functions.

Neurosteroid levels and metabolism have also been studied in the aged human brain (non-demented and Alzheimer's patients). A general trend toward decreased levels of all steroids was observed in all Alzheimer's patients¡¦ brain regions compared with controls. High levels of key proteins implicated in the formation of plaques and neurofibrillary tangles (fO-amyloid peptides, phosphorylated tau) were correlated with decreased brain levels of PREGS and DHEAS, suggesting a possible neuroprotective role of these neurosteroids in AD.

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