title: Selective Oestrogen Receptor Agonists Rescued Hippocampus Parameters in Male Spontaneously Hypertensive Rats.
abstract: Spontaneously hypertensive rats (SHR) show pronounced hippocampus alterations, including low brain-derived neurotrophic factor (BDNF) expression, reduced neurogenesis, astrogliosis and increased aromatase expression. These changes are reverted by treatment with 17β-oestradiol. To determine which oestradiol receptor (ER) type is involved in these neuroprotective effects, we used agonists of the ERα [propylpyrazole triol (PPT)] and the ERβ [diarylpropionitrite (DPN)] given over 2 weeks to 4-month-old male SHR. Wistar Kyoto normotensive rats served as controls. Using immunocytochemistry, we determined glial fibrillary protein (GFAP)+ astrocytes in the CA1, CA3 and hilus of the dentate gyrus of the hippocampus, aromatase immunostaining in the hilus, and doublecortin (DCX)+ neuronal progenitors in the inner granular zone of the dentate gyrus. Brain-derived neurotrophic factor mRNA was also measured in the hippocampus by the quantitative polymerase chain reaction. In SHR, PPT had no effect on blood pressure, decreased astrogliosis, slightly increased BDNF mRNA, had no effect on the number of DCX+ progenitors, and increased aromatase staining. Treatment with DPN decreased blood pressure, decreased astrogliosis, increased BDNF mRNA and DCX+ progenitors, and did not modify aromatase staining. We hypothesise that, although both receptor types may participate in the previously reported beneficial effects of 17β-oestradiol in SHR, receptor activation with DPN may preferentially facilitate BDNF mRNA expression and neurogenesis. The results of the present study may help in the design of ER-based neuroprotection for the encephalopathy of hypertension.
authors: 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: L
authors: L
authors: Pietranera
authors: Laboratory of Neuroendocrine Biochemistry, Instituto de Biología y Medicina Experimental, Buenos Aires, Argentina.
authors: J
authors: J
authors: Correa
authors: Laboratory of Neuroendocrine Biochemistry, Instituto de Biología y Medicina Experimental, Buenos Aires, Argentina.
authors: M E
authors: ME
authors: Brocca
authors: Laboratory of Neuroendocrine Biochemistry, Instituto de Biología y Medicina Experimental, Buenos Aires, Argentina.
authors: P
authors: P
authors: Roig
authors: Laboratory of Neuroendocrine Biochemistry, Instituto de Biología y Medicina Experimental, Buenos Aires, Argentina.
authors: A
authors: A
authors: Lima
authors: Laboratory of Neuroendocrinology, Instituto de Biología y Medicina Experimental, Buenos Aires, Argentina.
authors: N
authors: N
authors: Di Giorgio
authors: Instituto Cajal, Consejo Superior de Investigaciones Cientificas, Madrid, Spain.
authors: L M
authors: LM
authors: Garcia-Segura
authors: Laboratory of Neuroendocrine Biochemistry, Instituto de Biología y Medicina Experimental, Buenos Aires, Argentina. alejandrodenicola@gmail.com.|Department of Human Biochemistry, Faculty of Medicine, University of Buenos Aires, Buenos Aires, Argentina. alejandrodenicola@gmail.com.
authors: A F
authors: AF
authors: De Nicola
mesh_terms: D000818:Animals; D001141:Aromatase / Q000378:metabolism; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D000089662:Doublecortin Protein; D047628:Estrogen Receptor alpha / Q000819:agonists* / Q000502:physiology; D047629:Estrogen Receptor beta / Q000819:agonists* / Q000502:physiology; D005911:Gliosis; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D058953:Neural Stem Cells / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009570:Nitriles / Q000008:administration & dosage*; D009929:Organ Size; D010636:Phenols / Q000008:administration & dosage*; D010902:Pituitary Gland / Q000033:anatomy & histology / Q000187:drug effects; D011422:Propionates / Q000008:administration & dosage*; D011720:Pyrazoles / Q000008:administration & dosage*; D012333:RNA, Messenger / Q000378:metabolism; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013737:Testis / Q000033:anatomy & histology / Q000187:drug effects
chemical_list: C486182:2,3-bis(4-hydroxyphenyl)-propionitrile; D019208:Brain-Derived Neurotrophic Factor; C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D009570:Nitriles; D010636:Phenols; D011422:Propionates; D011720:Pyrazoles; D012333:RNA, Messenger; C486184:4,4',4''-(4-propyl-((1)H)-pyrazole-1,3,5-triyl) tris-phenol; D001141:Aromatase
keywords: hippocampus; hypertension; neurogenesis; oestrogen receptors