Neurosteroid Biosynthetic Pathway Changes in Substantia Nigra and Caudate Nucleus in Parkinson's Disease |
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| Authors: | Sabina Luchetti Koen Bossers Giovanni Vanni Frajese Dick F. Swaab |
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| Affiliation: | 1.Laboratory for Neuropsychiatric Disorders, Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands.; 2.Istituto Dermopatico Immacolata (IDI‐IRCCS), Santa Lucia Foundation Scientific Institute, Rome, Italy.; 3.Internal Medicine Department, Endocrinology lab, University of Rome “Tor Vergata”, Rome, Italy.; 4.Faculty of Motor Sciences, University of Cassino, Cassino, Italy. |
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| Abstract: | There is emerging evidence from animal studies for a neuroprotective role of sex steroids in neurodegenerative diseases, but studies in human brain are lacking. We have carried out an extensive study of the neurosteroid biosynthetic pathways in substantia nigra (SN), caudate nucleus (CN) and putamen (PU) of 7 Parkinson''s disease (PD) patients and 7 matched controls. The mRNA levels of 37 genes including neurosteroid biosynthetic enzymes, hormone receptors and the neurosteroid‐modulated γ‐amino‐butyric acid ‐A (GABA‐A) receptor subunits were analyzed by quantitative PCR (qPCR). In the SN, we found downregulation of 5α‐reductase type 1 (5α‐R1), sulfotransferase 2B1 (SULT2B1) and some GABA‐A receptor subunits (α4, β1) while in the CN, upregulation of 3α‐hydroxysteroid dehydrogenase type 3 (3α‐HSD3) and α4 GABA‐A receptor subunit (22‐fold) was observed. No significant differences were found in the PU. These data imply an involvement of pregnane steroids and changes in GABAergic neurotransmission in the neurodegenerative process and suggest that neurosteroids may deserve further investigation as potential therapeutic agents in PD. |
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| Keywords: | 3α lpha‐ hydroxysteroid dehydrogenase, 5α lphareductase, GABA‐ A receptors, gene expression, neurosteroids, Parkinson''s disease |
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