title: 17α-Oestradiol-induced neuroprotection in the brain of spontaneously hypertensive rats.
abstract: 17β-oestradiol is a powerful neuroprotective factor for the brain abnormalities of spontaneously hypertensive rats (SHR). 17α-Oestradiol, a nonfeminising isomer showing low affinity for oestrogen receptors, is also endowed with neuroprotective effects in vivo and in vitro. We therefore investigated whether treatment with 17α-oestradiol prevented pathological changes of the hippocampus and hypothalamus of SHR. We used 20-week-old male SHR with a blood pressure of approximately 170 mmHg receiving s.c. a single 800 μg pellet of 17α-oestradiol dissolved in cholesterol or vehicle only for 2 weeks Normotensive Wistar-Kyoto (WKY) rats were used as controls. 17α-Oestradiol did not modify blood pressure, serum prolactin, 17β-oestradiol levels or the weight of the testis and pituitary of SHR. In the brain, we analysed steroid effects on hippocampus Ki67+ proliferating cells, doublecortin (DCX) positive neuroblasts, glial fibrillary acidic protein (GFAP)+ astrocyte density, aromatase immunostaining and brain-derived neurotrophic factor (BDNF) mRNA. In the hypothalamus, we determined arginine vasopressin (AVP) mRNA. Treatment of SHR with 17α-oestradiol enhanced the number of Ki67+ in the subgranular zone and DCX+ cells in the inner granule cell layer of the dentate gyrus, increased BDNF mRNA in the CA1 region and gyrus dentatus, decreased GFAP+ astrogliosis in the CA1 subfield, and decreased hypothalamic AVP mRNA. Aromatase expression was unmodified. By contrast to SHR, normotensive WKY rats were unresponsive to 17α-oestradiol. These data indicate a role for 17α-oestradiol as a protective factor for the treatment of hypertensive encephalopathy. Furthermore, 17α-oestradiol is weakly oestrogenic in the periphery and can be used in males.
authors.affiliation: Laboratory of Neuroendocrine Biochemistry, Instituto de Biología y Medicina Experimental, Buenos Aires, Argentina; Department of Human Biochemistry, Faculty of Medicine, University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: L
authors.initials: L
authors.lastname: Pietranera
authors.forename: M E
authors.initials: ME
authors.lastname: Brocca
authors.forename: P
authors.initials: P
authors.lastname: Roig
authors.forename: A
authors.initials: A
authors.lastname: Lima
authors.forename: L M
authors.initials: LM
authors.lastname: Garcia-Segura
authors.forename: A F
authors.initials: AF
authors.lastname: De Nicola
mesh_terms: D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000187:drug effects*; D001923:Brain Chemistry / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D000089662:Doublecortin Protein; D004958:Estradiol / Q000494:pharmacology*; D005911:Gliosis / Q000473:pathology; D008297:Male; D055495:Neurogenesis / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; D018696:Neuroprotective Agents; D001127:Arginine Vasopressin; D004958:Estradiol
keywords: hippocampus; hypertension; hypothalamus; oestrogens