PMID- 20406233
OWN - NLM
STAT- MEDLINE
DCOM- 20101124
LR  - 20211020
IS  - 1750-3639 (Electronic)
IS  - 1015-6305 (Print)
IS  - 1015-6305 (Linking)
VI  - 20
IP  - 5
DP  - 2010 Sep
TI  - Neurosteroid biosynthetic pathway changes in substantia nigra and caudate nucleus 
      in Parkinson's disease.
PG  - 945-51
LID - 10.1111/j.1750-3639.2010.00396.x [doi]
AB  - 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 gamma-amino-butyric acid -A (GABA-A) receptor subunits 
      were analyzed by quantitative PCR (qPCR). In the SN, we found downregulation of 
      5alpha-reductase type 1 (5alpha-R1), sulfotransferase 2B1 (SULT2B1) and some 
      GABA-A receptor subunits (alpha4, beta1) while in the CN, upregulation of 
      3alpha-hydroxysteroid dehydrogenase type 3 (3alpha-HSD3) and alpha4 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.
FAU - Luchetti, Sabina
AU  - Luchetti S
AD  - Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and 
      Sciences, Amsterdam, The Netherlands. s.luchetti@nin.knaw.nl
FAU - Bossers, Koen
AU  - Bossers K
FAU - Frajese, Giovanni Vanni
AU  - Frajese GV
FAU - Swaab, Dick F
AU  - Swaab DF
LA  - eng
PT  - Journal Article
DEP - 20100319
PL  - Switzerland
TA  - Brain Pathol
JT  - Brain pathology (Zurich, Switzerland)
JID - 9216781
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Neurotransmitter Agents)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, GABA)
RN  - EC 2.8.2.- (Sulfotransferases)
RN  - EC 2.8.2.2 (SULT2B1 protein, human)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Case-Control Studies
MH  - Caudate Nucleus/*metabolism
MH  - DNA-Binding Proteins/genetics/metabolism
MH  - Female
MH  - Gene Expression Regulation/physiology
MH  - Humans
MH  - Male
MH  - Neural Pathways/metabolism
MH  - Neurotransmitter Agents/*metabolism
MH  - Parkinson Disease/*pathology
MH  - RNA, Messenger/metabolism
MH  - Receptors, GABA/genetics/metabolism
MH  - Substantia Nigra/*metabolism
MH  - Sulfotransferases/genetics/metabolism
PMC - PMC8094796
EDAT- 2010/04/22 06:00
MHDA- 2010/12/14 06:00
PMCR- 2010/03/19
CRDT- 2010/04/22 06:00
PHST- 2010/04/22 06:00 [entrez]
PHST- 2010/04/22 06:00 [pubmed]
PHST- 2010/12/14 06:00 [medline]
PHST- 2010/03/19 00:00 [pmc-release]
AID - BPA396 [pii]
AID - 10.1111/j.1750-3639.2010.00396.x [doi]
PST - ppublish
SO  - Brain Pathol. 2010 Sep;20(5):945-51. doi: 10.1111/j.1750-3639.2010.00396.x. Epub 
      2010 Mar 19.