Cargando…
The Angiotensin Type 1 Receptor Antagonist Losartan Prevents Ovariectomy-Induced Cognitive Dysfunction and Anxiety-Like Behavior in Long Evans Rats
Women who have bilateral oophorectomies prior to the age of natural menopause are at increased risk of developing mild cognitive decline, dementia, anxiety, and depressive type disorders. Clinical and animal studies indicate angiotensin type 1 receptor (AT(1)R) blockers (ARBs) have blood pressure (B...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer US
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7056686/ https://www.ncbi.nlm.nih.gov/pubmed/31637567 http://dx.doi.org/10.1007/s10571-019-00744-x |
_version_ | 1783503517536747520 |
---|---|
author | Campos, Glenda V. de Souza, Aline M. A. Ji, Hong West, Crystal A. Wu, Xie Lee, Dexter L. Aguilar, Brittany L. Forcelli, Patrick A. de Menezes, Rodrigo C. Sandberg, Kathryn |
author_facet | Campos, Glenda V. de Souza, Aline M. A. Ji, Hong West, Crystal A. Wu, Xie Lee, Dexter L. Aguilar, Brittany L. Forcelli, Patrick A. de Menezes, Rodrigo C. Sandberg, Kathryn |
author_sort | Campos, Glenda V. |
collection | PubMed |
description | Women who have bilateral oophorectomies prior to the age of natural menopause are at increased risk of developing mild cognitive decline, dementia, anxiety, and depressive type disorders. Clinical and animal studies indicate angiotensin type 1 receptor (AT(1)R) blockers (ARBs) have blood pressure (BP)-independent neuroprotective effects. To investigate the potential use of ARBs in normotensive women at increased risk of developing neurocognitive problems, we studied a rat model of bilateral oophorectomy. Long Evans rats were sham-operated (Sham) or ovariectomized (Ovx) at 3 months of age and immediately treated continuously with vehicle (Veh) or the ARB losartan (Los) for the duration of the experiment. In contrast to many hypertensive rat models, ovariectomy did not increase mean arterial pressure (MAP) in these normotensive rats. Ovariectomized rats spent less time in the open arms of the elevated plus maze (EPM) [(% total time): Veh, 34.1 ± 5.1 vs. Ovx, 18.7 ± 4.4; p < 0.05] and in the center of the open field (OF) [(s): Veh, 11.1 ± 1.7 vs. Ovx, 6.64 ± 1.1; p < 0.05]. They also had worse performance in the novel object recognition (NOR) test as evidenced by a reduction in the recognition index [Veh, 0.62 ± 0.04 vs. Ovx, 0.45 ± 0.03; p < 0.05]. These adverse effects of ovariectomy were prevented by Los. Losartan also reduced plasma corticosterone in Ovx rats compared to Veh treatment [(ng/mL): Ovx–Veh, 238 ± 20 vs. Ovx–Los, 119 ± 42; p < 0.05]. Ovariectomy increased AT(1)R mRNA expression in the CA3 region of the hippocampus (Hc) [(copies x 10(6)/µg RNA): Sham–Veh, 7.15 ± 0.87 vs. Ovx–Veh, 9.86 ± 1.7; p < 0.05]. These findings suggest the neuroprotective effects of this ARB in normotensive Ovx rats involve reduction of plasma corticosterone and blockade of increased AT(1)R activity in the hippocampus. These data suggest ARBs have therapeutic potential for normotensive women at increased risk of developing cognitive and behavioral dysfunction due to bilateral oophorectomy prior to the natural age of menopause. |
format | Online Article Text |
id | pubmed-7056686 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-70566862020-03-16 The Angiotensin Type 1 Receptor Antagonist Losartan Prevents Ovariectomy-Induced Cognitive Dysfunction and Anxiety-Like Behavior in Long Evans Rats Campos, Glenda V. de Souza, Aline M. A. Ji, Hong West, Crystal A. Wu, Xie Lee, Dexter L. Aguilar, Brittany L. Forcelli, Patrick A. de Menezes, Rodrigo C. Sandberg, Kathryn Cell Mol Neurobiol Original Research Women who have bilateral oophorectomies prior to the age of natural menopause are at increased risk of developing mild cognitive decline, dementia, anxiety, and depressive type disorders. Clinical and animal studies indicate angiotensin type 1 receptor (AT(1)R) blockers (ARBs) have blood pressure (BP)-independent neuroprotective effects. To investigate the potential use of ARBs in normotensive women at increased risk of developing neurocognitive problems, we studied a rat model of bilateral oophorectomy. Long Evans rats were sham-operated (Sham) or ovariectomized (Ovx) at 3 months of age and immediately treated continuously with vehicle (Veh) or the ARB losartan (Los) for the duration of the experiment. In contrast to many hypertensive rat models, ovariectomy did not increase mean arterial pressure (MAP) in these normotensive rats. Ovariectomized rats spent less time in the open arms of the elevated plus maze (EPM) [(% total time): Veh, 34.1 ± 5.1 vs. Ovx, 18.7 ± 4.4; p < 0.05] and in the center of the open field (OF) [(s): Veh, 11.1 ± 1.7 vs. Ovx, 6.64 ± 1.1; p < 0.05]. They also had worse performance in the novel object recognition (NOR) test as evidenced by a reduction in the recognition index [Veh, 0.62 ± 0.04 vs. Ovx, 0.45 ± 0.03; p < 0.05]. These adverse effects of ovariectomy were prevented by Los. Losartan also reduced plasma corticosterone in Ovx rats compared to Veh treatment [(ng/mL): Ovx–Veh, 238 ± 20 vs. Ovx–Los, 119 ± 42; p < 0.05]. Ovariectomy increased AT(1)R mRNA expression in the CA3 region of the hippocampus (Hc) [(copies x 10(6)/µg RNA): Sham–Veh, 7.15 ± 0.87 vs. Ovx–Veh, 9.86 ± 1.7; p < 0.05]. These findings suggest the neuroprotective effects of this ARB in normotensive Ovx rats involve reduction of plasma corticosterone and blockade of increased AT(1)R activity in the hippocampus. These data suggest ARBs have therapeutic potential for normotensive women at increased risk of developing cognitive and behavioral dysfunction due to bilateral oophorectomy prior to the natural age of menopause. Springer US 2019-10-21 2020 /pmc/articles/PMC7056686/ /pubmed/31637567 http://dx.doi.org/10.1007/s10571-019-00744-x Text en © The Author(s) 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Original Research Campos, Glenda V. de Souza, Aline M. A. Ji, Hong West, Crystal A. Wu, Xie Lee, Dexter L. Aguilar, Brittany L. Forcelli, Patrick A. de Menezes, Rodrigo C. Sandberg, Kathryn The Angiotensin Type 1 Receptor Antagonist Losartan Prevents Ovariectomy-Induced Cognitive Dysfunction and Anxiety-Like Behavior in Long Evans Rats |
title | The Angiotensin Type 1 Receptor Antagonist Losartan Prevents Ovariectomy-Induced Cognitive Dysfunction and Anxiety-Like Behavior in Long Evans Rats |
title_full | The Angiotensin Type 1 Receptor Antagonist Losartan Prevents Ovariectomy-Induced Cognitive Dysfunction and Anxiety-Like Behavior in Long Evans Rats |
title_fullStr | The Angiotensin Type 1 Receptor Antagonist Losartan Prevents Ovariectomy-Induced Cognitive Dysfunction and Anxiety-Like Behavior in Long Evans Rats |
title_full_unstemmed | The Angiotensin Type 1 Receptor Antagonist Losartan Prevents Ovariectomy-Induced Cognitive Dysfunction and Anxiety-Like Behavior in Long Evans Rats |
title_short | The Angiotensin Type 1 Receptor Antagonist Losartan Prevents Ovariectomy-Induced Cognitive Dysfunction and Anxiety-Like Behavior in Long Evans Rats |
title_sort | angiotensin type 1 receptor antagonist losartan prevents ovariectomy-induced cognitive dysfunction and anxiety-like behavior in long evans rats |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7056686/ https://www.ncbi.nlm.nih.gov/pubmed/31637567 http://dx.doi.org/10.1007/s10571-019-00744-x |
work_keys_str_mv | AT camposglendav theangiotensintype1receptorantagonistlosartanpreventsovariectomyinducedcognitivedysfunctionandanxietylikebehaviorinlongevansrats AT desouzaalinema theangiotensintype1receptorantagonistlosartanpreventsovariectomyinducedcognitivedysfunctionandanxietylikebehaviorinlongevansrats AT jihong theangiotensintype1receptorantagonistlosartanpreventsovariectomyinducedcognitivedysfunctionandanxietylikebehaviorinlongevansrats AT westcrystala theangiotensintype1receptorantagonistlosartanpreventsovariectomyinducedcognitivedysfunctionandanxietylikebehaviorinlongevansrats AT wuxie theangiotensintype1receptorantagonistlosartanpreventsovariectomyinducedcognitivedysfunctionandanxietylikebehaviorinlongevansrats AT leedexterl theangiotensintype1receptorantagonistlosartanpreventsovariectomyinducedcognitivedysfunctionandanxietylikebehaviorinlongevansrats AT aguilarbrittanyl theangiotensintype1receptorantagonistlosartanpreventsovariectomyinducedcognitivedysfunctionandanxietylikebehaviorinlongevansrats AT forcellipatricka theangiotensintype1receptorantagonistlosartanpreventsovariectomyinducedcognitivedysfunctionandanxietylikebehaviorinlongevansrats AT demenezesrodrigoc theangiotensintype1receptorantagonistlosartanpreventsovariectomyinducedcognitivedysfunctionandanxietylikebehaviorinlongevansrats AT sandbergkathryn theangiotensintype1receptorantagonistlosartanpreventsovariectomyinducedcognitivedysfunctionandanxietylikebehaviorinlongevansrats AT camposglendav angiotensintype1receptorantagonistlosartanpreventsovariectomyinducedcognitivedysfunctionandanxietylikebehaviorinlongevansrats AT desouzaalinema angiotensintype1receptorantagonistlosartanpreventsovariectomyinducedcognitivedysfunctionandanxietylikebehaviorinlongevansrats AT jihong angiotensintype1receptorantagonistlosartanpreventsovariectomyinducedcognitivedysfunctionandanxietylikebehaviorinlongevansrats AT westcrystala angiotensintype1receptorantagonistlosartanpreventsovariectomyinducedcognitivedysfunctionandanxietylikebehaviorinlongevansrats AT wuxie angiotensintype1receptorantagonistlosartanpreventsovariectomyinducedcognitivedysfunctionandanxietylikebehaviorinlongevansrats AT leedexterl angiotensintype1receptorantagonistlosartanpreventsovariectomyinducedcognitivedysfunctionandanxietylikebehaviorinlongevansrats AT aguilarbrittanyl angiotensintype1receptorantagonistlosartanpreventsovariectomyinducedcognitivedysfunctionandanxietylikebehaviorinlongevansrats AT forcellipatricka angiotensintype1receptorantagonistlosartanpreventsovariectomyinducedcognitivedysfunctionandanxietylikebehaviorinlongevansrats AT demenezesrodrigoc angiotensintype1receptorantagonistlosartanpreventsovariectomyinducedcognitivedysfunctionandanxietylikebehaviorinlongevansrats AT sandbergkathryn angiotensintype1receptorantagonistlosartanpreventsovariectomyinducedcognitivedysfunctionandanxietylikebehaviorinlongevansrats |