Neuroactive steroid levels in plasma and cerebrospinal fluid of male multiple sclerosis patients.
Neuroactive steroid family includes molecules synthesized in peripheral glands (i.e., hormonal steroids) and directly in the nervous system (i.e., neurosteroids) which are key regulators of the nervous function. As already reported in clinical and experimental studies, neurodegenerative diseases affect the levels of neuroactive steroids. However, a careful analysis comparing the levels of these molecules in cerebrospinal fluid (CSF) and in plasma of multiple sclerosis (MS) patients is still missing. To this aim, the levels of neuroactive steroids were evaluated by liquid chromatography-tandem mass spectrometry in CSF and plasma of male adults affected by Relapsing-Remitting MS and compared with those collected in control patients. An increase in pregnenolone and isopregnanolone levels associated with a decrease in progesterone metabolites, dihydroprogesterone, and tetrahydroprogesterone was observed in CSF of MS patients. Moreover, an increase of 5α-androstane-3α,17β-diol and of 17β-estradiol levels associated with a decrease of dihydrotestosterone also occurred. In plasma, an increase in pregnenolone, progesterone, and dihydrotestosterone and a decrease in dihydroprogesterone and tetrahydroprogesterone levels were reported. This study shows for the first time that the levels of several neuroactive steroids, and particularly those of progesterone and testosterone metabolites, are deeply affected in CSF of relapsing-remitting MS male patients. We here demonstrated that, the cerebrospinal fluid and plasma levels of several neuroactive steroids are modified in relapsing remitting multiple sclerosis male patients. Interestingly, we reported for the first time that, the levels of progesterone and testosterone metabolites are deeply affected in cerebrospinal fluid. These findings may have an important relevance in therapeutic and/or diagnostic field of multiple sclerosis.
Department of Pharmacological and Biomolecular Sciences - Center of Excellence on Neurodegenerative Diseases, Università degli Studi di Milano, Milano, Italy.
Donatella
D
Caruso
Marta
M
Melis
Giuseppe
G
Fenu
Silvia
S
Giatti
Simone
S
Romano
Maria
M
Grimoldi
Donatella
D
Crippa
Maria Giovanna
MG
Marrosu
Guido
G
Cavaletti
Roberto Cosimo
RC
Melcangi
D000328:Adult; D001812:Blood-Brain Barrier / Q000473:pathology; D002138:Calibration; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D007525:Isoelectric Focusing; D008297:Male; D009103:Multiple Sclerosis / Q000097:blood* / Q000134:cerebrospinal fluid*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood / Q000134:cerebrospinal fluid; D013129:Spinal Puncture; D013256:Steroids / Q000097:blood* / Q000134:cerebrospinal fluid*; D053719:Tandem Mass Spectrometry
D013256:Steroids
liquid chromatography-tandem mass spectrometry; neurosteroids; pregnenolone; progesterone metabolites; relapsing-remitting multiple sclerosis; testosterone metabolites