title: Comparison of plasma and cerebrospinal fluid levels of neuroactive steroids with their brain, spinal cord and peripheral nerve levels in male and female rats.
abstract: Physiological changes and pathological alterations in the nervous system of rodents are associated with modifications in the levels of neuroactive steroids in the brain, spinal cord and/or peripheral nerves. Measures of tissue levels of steroids in the nervous system present serious limitations for human studies and for longitudinal studies in animals. In this study we have explored whether levels of neuroactive steroids in plasma and the cerebrospinal fluid reflect their levels in neural tissues. To this aim, we have evaluated by liquid chromatography-tandem mass spectrometry the levels of several neuroactive steroids in plasma, cerebrospinal fluid, cerebral cortex, cerebellum, hippocampus, spinal cord and sciatic nerve of male and female rats. Data indicate that plasma and cerebrospinal fluid levels of steroids do not fully reflect their tissue levels. However, the interindividual variations in the levels of all the steroids assessed, with the exception of dehydroepiandrosterone, showed a positive correlation in plasma and cerebral cortex. Most steroids also showed a positive correlation in plasma and the cerebellum, the spinal cord and the sciatic nerve. In the hippocampus, the levels of tetrahydroprogesterone, testosterone and testosterone metabolites showed a significant positive correlation with their respective levels in plasma. The cerebrospinal fluid levels of some steroids, such as testosterone and dihydrotestosterone, showed a full correlation with tissue levels. In addition, cerebrospinal fluid levels of pregnenolone, progesterone, and 17β-estradiol showed a positive correlation with their corresponding levels in the majority of the neural structures analyzed. These findings suggest that the levels of some neuroactive steroids in cerebrospinal fluid as well as in plasma may be valuable to predict their levels in the nervous system.
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, Center of Excellence on Neurodegenerative Diseases, Università degli Studi di Milano, Milano, Italy.
authors.forename: Donatella
authors.initials: D
authors.lastname: Caruso
authors.forename: Marzia
authors.initials: M
authors.lastname: Pesaresi
authors.forename: Federico
authors.initials: F
authors.lastname: Abbiati
authors.forename: Donato
authors.initials: D
authors.lastname: Calabrese
authors.forename: Silvia
authors.initials: S
authors.lastname: Giatti
authors.forename: Luis Miguel
authors.initials: LM
authors.lastname: Garcia-Segura
authors.forename: Roberto Cosimo
authors.initials: RC
authors.lastname: Melcangi
mesh_terms: D000818:Animals; D001774:Blood Chemical Analysis / Q000592:standards; D001921:Brain / Q000378:metabolism; D001923:Brain Chemistry; D002853:Chromatography, Liquid / Q000592:standards; D005260:Female; D008297:Male; D018377:Neurotransmitter Agents / Q000097:blood* / Q000134:cerebrospinal fluid*; D010525:Peripheral Nerves / Q000737:chemistry* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D013116:Spinal Cord / Q000737:chemistry* / Q000378:metabolism; D013256:Steroids / Q000032:analysis / Q000378:metabolism; D053719:Tandem Mass Spectrometry / Q000592:standards
chemical_list: D018377:Neurotransmitter Agents; D013256:Steroids
keywords: Metabolism; Neurosteroids; Pregnenolone; Progesterone; Testosterone