TY - JOUR
T1 - Modifications of neuroactive steroid levels in an experimental model of nigrostriatal degeneration
T2 - Potential relevance to the pathophysiology of Parkinson's disease
AU - Melcangi, Roberto Cosimo
AU - Caruso, Donatella
AU - Levandis, Giovanna
AU - Abbiati, Federico
AU - Armentero, Marie Therese
AU - Blandini, Fabio
PY - 2012/1
Y1 - 2012/1
N2 - 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.
AB - 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.
KW - 6-Hydroxydopamine
KW - Cerebral cortex
KW - Dihydroprogesterone
KW - Isopregnanolone
KW - Pregnenolone
KW - Striatum
UR - http://www.scopus.com/inward/record.url?scp=84858826382&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84858826382&partnerID=8YFLogxK
U2 - 10.1007/s12031-011-9570-y
DO - 10.1007/s12031-011-9570-y
M3 - Article
C2 - 21671084
AN - SCOPUS:84858826382
VL - 46
SP - 177
EP - 183
JO - Journal of Molecular Neuroscience
JF - Journal of Molecular Neuroscience
SN - 0895-8696
IS - 1
ER -