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Potential neuroprotective effect of androst-5-ene-3β, 17β-diol (ADIOL) on the striatum, and substantia nigra in Parkinson's disease rat model.
J Cell Physiol. 2018 08; 233(8):5981-6000.JC

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disorder with behavioral and motor abnormalities. Androst-5-ene-3β, 17β-diol (ADIOL), an estrogen receptor (ER) β agonist, was found to mediate a transrepressive mechanism that selectively modulates the extent of neuroinflammation and, in turn, neurodegeneration. In consensus, ERβ polymorphism was more frequently detected in early-onset PD patients. Thus, in an approach to elucidate the role of ERβ 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-κB), 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 α-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.

Authors+Show Affiliations

Faculty of Pharmacy, Department of Pharmacology and Toxicology, Misr International University (MIU), Cairo, Egypt.Faculty of Pharmacy, Department of Pharmacology and Toxicology, Ain Shams University, Cairo, Egypt.Faculty of Pharmacy, Department of Biochemistry, Misr International University (MIU), Cairo, Egypt.Faculty of Medicine, Department of Histology and Cell Biology, Ain Shams University, Cairo, Egypt.Faculty of Medicine, Department of Pharmacology, Ain Shams University, Cairo, Egypt.Faculty of Pharmacy, Department of Pharmacology and Toxicology, Ain Shams University, Cairo, Egypt.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29266208

Citation

Salama, Rania M., et al. "Potential Neuroprotective Effect of Androst-5-ene-3β, 17β-diol (ADIOL) On the Striatum, and Substantia Nigra in Parkinson's Disease Rat Model." Journal of Cellular Physiology, vol. 233, no. 8, 2018, pp. 5981-6000.
Salama RM, Tadros MG, Schaalan MF, et al. Potential neuroprotective effect of androst-5-ene-3β, 17β-diol (ADIOL) on the striatum, and substantia nigra in Parkinson's disease rat model. J Cell Physiol. 2018;233(8):5981-6000.
Salama, R. M., Tadros, M. G., Schaalan, M. F., Bahaa, N., Abdel-Tawab, A. M., & Khalifa, A. E. (2018). Potential neuroprotective effect of androst-5-ene-3β, 17β-diol (ADIOL) on the striatum, and substantia nigra in Parkinson's disease rat model. Journal of Cellular Physiology, 233(8), 5981-6000. https://doi.org/10.1002/jcp.26412
Salama RM, et al. Potential Neuroprotective Effect of Androst-5-ene-3β, 17β-diol (ADIOL) On the Striatum, and Substantia Nigra in Parkinson's Disease Rat Model. J Cell Physiol. 2018;233(8):5981-6000. PubMed PMID: 29266208.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Potential neuroprotective effect of androst-5-ene-3β, 17β-diol (ADIOL) on the striatum, and substantia nigra in Parkinson's disease rat model. AU - Salama,Rania M, AU - Tadros,Mariane G, AU - Schaalan,Mona F, AU - Bahaa,Nevine, AU - Abdel-Tawab,Ahmed M, AU - Khalifa,Amani E, Y1 - 2018/02/27/ PY - 2017/09/02/received PY - 2017/12/19/accepted PY - 2017/12/22/pubmed PY - 2019/9/24/medline PY - 2017/12/22/entrez KW - 17β-diol KW - Androst-5-ene-3β KW - Parkinson's disease KW - estrogen receptor KW - neurodegeneration KW - neuroinflammation KW - rotenone SP - 5981 EP - 6000 JF - Journal of cellular physiology JO - J Cell Physiol VL - 233 IS - 8 N2 - Parkinson's disease (PD) is a progressive neurodegenerative disorder with behavioral and motor abnormalities. Androst-5-ene-3β, 17β-diol (ADIOL), an estrogen receptor (ER) β agonist, was found to mediate a transrepressive mechanism that selectively modulates the extent of neuroinflammation and, in turn, neurodegeneration. In consensus, ERβ polymorphism was more frequently detected in early-onset PD patients. Thus, in an approach to elucidate the role of ERβ 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-κB), 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 α-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. SN - 1097-4652 UR - https://www.unboundmedicine.com/medline/citation/29266208/Potential_neuroprotective_effect_of_androst_5_ene_3β_17β_diol__ADIOL__on_the_striatum_and_substantia_nigra_in_Parkinson's_disease_rat_model_ DB - PRIME DP - Unbound Medicine ER -