title: Modifications of neuroactive steroid levels in an experimental model of nigrostriatal degeneration: potential relevance to the pathophysiology of Parkinson's disease.
abstract: An important link between neuroactive steroids and neurodegenerative disorders has recently been suggested. Indeed, in several neurodegenerative experimental models the levels of neuroactive steroids are affected and their administration exerts neuroprotective effects. However, scarce information has so far been obtained on the neuroactive steroid levels present in Parkinson's disease. To this aim, using an experimental model of loss of nigrostriatal dopaminergic neurons obtained by stereotaxic injection of the neurotoxin 6-hydroxydopamine (6-OHDA), we evaluated by liquid chromatography tandem mass spectrometry the levels of several neuroactive steroids in the striatum and cerebral cortex of 6-OHDA-lesioned male rats. Among the neuroactive steroid levels assessed (i.e., pregnenolone, progesterone, dihydroprogesterone, tetrahydroprogesterone, isopregnanolone, testosterone, dihydrotestosterone, 3α-diol, dehydroepiandrosterone, 17α-estradiol, and 17β-estradiol), we observed a significant decrease of pregnenolone in the striatum. A similar effect was also observed on the levels of dihydroprogesterone present in this cerebral area and also in the cerebral cortex. Interestingly, an increase of isopregnanolone also occurred in the striatum and in the cerebral cortex. Altogether, these results suggesting that progesterone metabolism is affected in an experimental model of Parkinson's disease further highlight the link between neuroactive steroids and the neurodegenerative diseases.
authors.affiliation: Department of Endocrinology, Pathophysiology and Applied Biology-Center of Excellence on Neurodegenerative Diseases, Università degli Studi di Milano, Via Balzaretti 9, 20133, Milan, Italy. roberto.melcangi@unimi.it
authors.forename: Roberto Cosimo
authors.initials: RC
authors.lastname: Melcangi
authors.forename: Donatella
authors.initials: D
authors.lastname: Caruso
authors.forename: Giovanna
authors.initials: G
authors.lastname: Levandis
authors.forename: Federico
authors.initials: F
authors.lastname: Abbiati
authors.forename: Marie-Therese
authors.initials: MT
authors.lastname: Armentero
authors.forename: Fabio
authors.initials: F
authors.lastname: Blandini
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D003342:Corpus Striatum / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D008297:Male; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D016627:Oxidopamine / Q000633:toxicity; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology*; D051381:Rats; D013256:Steroids / Q000378:metabolism*; D013378:Substantia Nigra / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D013565:Sympatholytics / Q000633:toxicity
chemical_list: D013256:Steroids; D013565:Sympatholytics; D016627:Oxidopamine