title: Genistein improves sensorimotor gating: Mechanisms related to its neuroprotective effects on the striatum.
abstract: Huntington's disease (HD) is a neurodegenerative disorder, characterized by selective atrophy in the striatum, particularly the medium spiny GABAergic efferent neurons. This results in striatal sensorimotor gating deficits. Systemic administration of 3-nitropropionic acid (3-NPA) produces selective lesions mimicking those of HD. Males were found to be more susceptible to 3-NPA-induced neurotoxicity than females, suggesting neuroprotective effects of estrogens. Phytoestrogens, including genistein, are good estrogenic alternatives that keep their beneficial effects on non-reproductive organs and lack the potential hazardous side effects. The current study was designed to investigate the potential beneficial effects of genistein in 3-NPA-induced HD in ovariectomized rats. Results showed that 3-NPA (20 mg/kg) administration caused significant disruption of the rats' locomotor activity and prepulse inhibition. In addition, it decreased striatal ATP levels and increased oxidative stress, inflammatory and apoptotic markers with striatal focal hemorrhage and gliosis. Pretreatment with 17β-estradiol (2.5 mg/kg) or genistein (20 mg/kg) led to a significant improvement of behavioral parameters, increased ATP production, decreased oxidative stress, attenuated inflammation and apoptosis. Therefore, this study suggests potential neuroprotective effects of genistein in ovariectomized rats challenged with 3-NPA.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
authors.forename: Esther T
authors.initials: ET
authors.lastname: Menze
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Esmat
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
authors.forename: Mariane G
authors.initials: MG
authors.lastname: Tadros
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
authors.forename: Amani E
authors.initials: AE
authors.lastname: Khalifa
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt. Electronic address: abnaim@yahoo.com.
authors.forename: Ashraf B
authors.initials: AB
authors.lastname: Abdel-Naim
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D004958:Estradiol / Q000008:administration & dosage; D004967:Estrogens / Q000008:administration & dosage; D005260:Female; D019833:Genistein / Q000008:administration & dosage*; D006816:Huntington Disease / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology* / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000378:metabolism; D008124:Locomotion; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D009574:Nitro Compounds; D018384:Oxidative Stress; D048789:Phytoestrogens / Q000008:administration & dosage*; D065808:Prepulse Inhibition / Q000187:drug effects*; D011422:Propionates; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000975:Antioxidants; D004967:Estrogens; D018836:Inflammation Mediators; D018696:Neuroprotective Agents; D009574:Nitro Compounds; D048789:Phytoestrogens; D011422:Propionates; D004958:Estradiol; D000255:Adenosine Triphosphate; D019833:Genistein; D015232:Dinoprostone; C015392:3-nitropropionic acid
keywords: 17β-estradiol; 3-Nitropropionic acid; Genistein; Huntington's disease; Prepulse inhibition