title: Estrogens are neuroprotective factors for hypertensive encephalopathy.
abstract: Estrogens are neuroprotective factors for brain diseases, including hypertensive encephalopathy. In particular, the hippocampus is highly damaged by high blood pressure, with several hippocampus functions being altered in humans and animal models of hypertension. Working with a genetic model of primary hypertension, the spontaneously hypertensive rat (SHR), we have shown that SHR present decreased dentate gyrus neurogenesis, astrogliosis, low expression of brain derived neurotrophic factor (BDNF), decreased number of neurons in the hilus of the dentate gyrus, increased basal levels of the estrogen-synthesizing enzyme aromatase, and atrophic dendritic arbor with low spine density in the CA1 region compared to normotensive Wistar Kyoto (WKY) ratsl. Changes also occur in the hypothalamus of SHR, with increased expression of the hypertensinogenic peptide arginine vasopressin (AVP) and its V1b receptor. Following chronic estradiol treatment, SHR show decreased blood pressure, enhanced hippocampus neurogenesis, decreased the reactive astrogliosis, increased BDNF mRNA and protein expression in the dentate gyrus, increased neuronal number in the hilus of the dentate gyrus, further increased the hyperexpression of aromatase and replaced spine number with remodeling of the dendritic arbor of the CA1 region. We have detected by qPCR the estradiol receptors ERα and ERβ in hippocampus from both SHR and WKY rats, suggesting direct effects of estradiol on brain cells. We hypothesize that a combination of exogenously given estrogens plus those locally synthesized by estradiol-stimulated aromatase may better alleviate the hippocampal and hypothalamic encephalopathy of SHR. This article is part of a Special Issue entitled "Sex steroids and brain disorders".
authors.affiliation: Laboratory of Neuroendocrine Biochemistry, Instituto de Biología y Medicina Experimental, Obligado 2490, 1428 Buenos Aires, Argentina; Department of Human Biochemistry, Faculty of Medicine, University of Buenos Aires, Paraguay 2155, 1425 Buenos Aires, Argentina.
authors.forename: Luciana
authors.initials: L
authors.lastname: Pietranera
authors.affiliation: Laboratory of Neuroendocrine Biochemistry, Instituto de Biología y Medicina Experimental, Obligado 2490, 1428 Buenos Aires, Argentina.
authors.forename: Maria Elvira
authors.initials: ME
authors.lastname: Brocca
authors.affiliation: Laboratory of Neuroendocrine Biochemistry, Instituto de Biología y Medicina Experimental, Obligado 2490, 1428 Buenos Aires, Argentina.
authors.forename: Paulina
authors.initials: P
authors.lastname: Roig
authors.affiliation: Laboratory of Neuroendocrine Biochemistry, Instituto de Biología y Medicina Experimental, Obligado 2490, 1428 Buenos Aires, Argentina.
authors.forename: Analia
authors.initials: A
authors.lastname: Lima
authors.affiliation: Instituto Cajal, Consejo Superior de Investigaciones Cientificas, Avenida Doctor Arce 37, E-28002 Madrid, Spain.
authors.forename: Luis Miguel
authors.initials: LM
authors.lastname: Garcia-Segura
authors.affiliation: Laboratory of Neuroendocrine Biochemistry, Instituto de Biología y Medicina Experimental, Obligado 2490, 1428 Buenos Aires, Argentina; Department of Human Biochemistry, Faculty of Medicine, University of Buenos Aires, Paraguay 2155, 1425 Buenos Aires, Argentina. Electronic address: alejandrodenicola@gmail.com.
authors.forename: Alejandro F
authors.initials: AF
authors.lastname: De Nicola
mesh_terms: D000818:Animals; D001141:Aromatase / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology*; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D020343:Hypertensive Encephalopathy / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D018696:Neuroprotective Agents; D004958:Estradiol; D001141:Aromatase
keywords: Dendrites; Estradiol; Hypertensive rats; Neurogenesis, Astrogliosis, Growth factor; Neuroprotection; Spinogenesis; Vasopressin