title: Neuroprotective effect of the aminoestrogen prolame against impairment of learning and memory skills in rats injected with amyloid-β-25-35 into the hippocampus.
abstract: Alzheimer's disease (AD) is a neurodegenerative disorder caused by the deposition of the amyloid-beta peptide (Aβ) in senile plaques and cerebral vasculature. Its neurotoxic mechanisms are associated with the generation of oxidative stress and reactive astrogliosis that cause neuronal death and memory impairment. Estrogens reduce the rate of Azheimer's disease because of their antioxidant activity. Prolame (N-(3-hydroxy-1,3,5(10)-estratrien-17β-yl)-3-hydroxypropylamine) is an aminoestrogen with estrogenic and antithrombotic effects. In our study we evaluated the role of prolame on Aβ(25-35)-caused oxidative stress, reactive astrogliosis, and impairment of spatial memory(.) The Aβ(25-35) (100 μM/μl) or vehicle was injected into the CA1 subfield of the hippocampus of the rat. The subcutaneous injection of prolame (400 μl, 50 nM) or sesame oil (400 μl) started 1 day before the Aβ(25-35) injection and was continued for another 29 days. The results showed a significant impairment of spatial memory evident 30 days after the Aβ(25-35) injection. The prolame treatment significantly reduced spatial-memory impairment and decreased lipid peroxidation, reactive oxygen species, and reactive gliosis. It also restored the eNOS and nNOS expression to normal levels. In conclusion the aminoestrogen prolame should be considered as an alternative in the treatment of Alzheimer's disease.
authors.affiliation: Laboratorio de Neurofarmacología, Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Puebla 72570, Mexico.
authors.forename: Daniel
authors.initials: D
authors.lastname: Limón
authors.forename: Alfonso
authors.initials: A
authors.lastname: Díaz
authors.forename: Monserrat
authors.initials: M
authors.lastname: Hernandez
authors.forename: Juan M
authors.initials: JM
authors.lastname: Fernandez-G
authors.forename: Ana C
authors.initials: AC
authors.lastname: Torres-Martínez
authors.forename: Francisca
authors.initials: F
authors.lastname: Pérez-Severiano
authors.forename: Erika P
authors.initials: EP
authors.lastname: Rendón-Huerta
authors.forename: Luis F
authors.initials: LF
authors.lastname: Montaño
authors.forename: Jorge
authors.initials: J
authors.lastname: Guevara
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000633:toxicity; D000818:Animals; D004195:Disease Models, Animal; D004963:Estrenes / Q000008:administration & dosage / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology; D007859:Learning Disabilities / Q000188:drug therapy* / Q000503:physiopathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy* / Q000503:physiopathology; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010446:Peptide Fragments / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D004963:Estrenes; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; C074636:amyloid beta-protein (25-35); C047867:prolame; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III