PMID- 29266208
OWN - NLM
STAT- MEDLINE
DCOM- 20190923
LR  - 20190923
IS  - 1097-4652 (Electronic)
IS  - 0021-9541 (Linking)
VI  - 233
IP  - 8
DP  - 2018 Aug
TI  - Potential neuroprotective effect of androst-5-ene-3beta, 17beta-diol (ADIOL) on the 
      striatum, and substantia nigra in Parkinson's disease rat model.
PG  - 5981-6000
LID - 10.1002/jcp.26412 [doi]
AB  - Parkinson's disease (PD) is a progressive neurodegenerative disorder with 
      behavioral and motor abnormalities. Androst-5-ene-3beta, 17beta-diol (ADIOL), an 
      estrogen receptor (ER) beta agonist, was found to mediate a transrepressive 
      mechanism that selectively modulates the extent of neuroinflammation and, in 
      turn, neurodegeneration. In consensus, ERbeta polymorphism was more frequently 
      detected in early-onset PD patients. Thus, in an approach to elucidate the role 
      of ERbeta agonists on PD, our study was designed to investigate the possible 
      neuroprotective effect of ADIOL, in three dose levels (0.35, 3.5, 35 mg/kg/day), 
      against rotenone (ROT)-induced PD rat model. Amelioration in striatal dopamine 
      (DA), nuclear factor-kappa B (NF-kappaB), and the expression of down-stream 
      inflammatory mediators, as well as apoptotic markers were observed in the 
      striatum and substantia nigra (SN) upon pre-treatment with the three doses of 
      ADIOL. Similarly, light microscopy (LM) examination revealed declined 
      degeneration of neurons upon pretreatment with ADIOL. Significant improvement in 
      nigral tyrosine hydroxylase (TH) and reduction of nigral alpha-synuclein densities 
      were also detected after ADIOL pre-treatment with better results frequently 
      achieved with the middle dose (3.5 mg/kg/day). The middle dose of ADIOL showed 
      behavioral improvement, with elevation in the ATP level, which was emphasized by 
      the improvement in mitochondrial integrity observed upon electron microscopy (EM) 
      examination. In conclusion, the present study confirmed for the first time the 
      ability of ADIOL to protect against neuroinflammation and, in turn, 
      neurodegeneration process and motor dysfunction in PD animal model, which was 
      more obviously observed with the middle dose.
CI  - (c) 2017 Wiley Periodicals, Inc.
FAU - Salama, Rania M
AU  - Salama RM
AUID- ORCID: 0000-0002-1873-6222
AD  - Faculty of Pharmacy, Department of Pharmacology and Toxicology, Misr 
      International University (MIU), Cairo, Egypt.
FAU - Tadros, Mariane G
AU  - Tadros MG
AD  - Faculty of Pharmacy, Department of Pharmacology and Toxicology, Ain Shams 
      University, Cairo, Egypt.
FAU - Schaalan, Mona F
AU  - Schaalan MF
AUID- ORCID: 0000-0002-8569-689X
AD  - Faculty of Pharmacy, Department of Biochemistry, Misr International University 
      (MIU), Cairo, Egypt.
FAU - Bahaa, Nevine
AU  - Bahaa N
AD  - Faculty of Medicine, Department of Histology and Cell Biology, Ain Shams 
      University, Cairo, Egypt.
FAU - Abdel-Tawab, Ahmed M
AU  - Abdel-Tawab AM
AD  - Faculty of Medicine, Department of Pharmacology, Ain Shams University, Cairo, 
      Egypt.
FAU - Khalifa, Amani E
AU  - Khalifa AE
AD  - Faculty of Pharmacy, Department of Pharmacology and Toxicology, Ain Shams 
      University, Cairo, Egypt.
LA  - eng
PT  - Journal Article
DEP - 20180227
PL  - United States
TA  - J Cell Physiol
JT  - Journal of cellular physiology
JID - 0050222
RN  - 0 (Estrogen Receptor beta)
RN  - 0 (Inflammation Mediators)
RN  - 0 (NF-kappa B)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (alpha-Synuclein)
RN  - 03L9OT429T (Rotenone)
RN  - 95PS51EMXY (Androstenediol)
RN  - EC 1.14.16.2 (Tyrosine 3-Monooxygenase)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - Androstenediol/*pharmacology
MH  - Animals
MH  - Corpus Striatum/*drug effects/metabolism
MH  - Disease Models, Animal
MH  - Dopamine/metabolism
MH  - Estrogen Receptor beta/metabolism
MH  - Inflammation Mediators/metabolism
MH  - Male
MH  - Motor Activity/drug effects
MH  - NF-kappa B/metabolism
MH  - Neurons/drug effects/metabolism
MH  - Neuroprotective Agents/*pharmacology
MH  - Parkinson Disease/*drug therapy/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Rotenone/pharmacology
MH  - Substantia Nigra/*drug effects/metabolism
MH  - Tyrosine 3-Monooxygenase/metabolism
MH  - alpha-Synuclein/metabolism
OTO - NOTNLM
OT  - 17beta-diol
OT  - Androst-5-ene-3beta
OT  - Parkinson's disease
OT  - estrogen receptor
OT  - neurodegeneration
OT  - neuroinflammation
OT  - rotenone
EDAT- 2017/12/22 06:00
MHDA- 2019/09/24 06:00
CRDT- 2017/12/22 06:00
PHST- 2017/09/02 00:00 [received]
PHST- 2017/12/19 00:00 [accepted]
PHST- 2017/12/22 06:00 [pubmed]
PHST- 2019/09/24 06:00 [medline]
PHST- 2017/12/22 06:00 [entrez]
AID - 10.1002/jcp.26412 [doi]
PST - ppublish
SO  - J Cell Physiol. 2018 Aug;233(8):5981-6000. doi: 10.1002/jcp.26412. Epub 2018 Feb 
      27.