Evidence map›Paper›PMID 36398458›Full record

ArticleClinical and experimental pharmacology & physiology2023

Angiotensin receptor blockade with olmesartan alleviates brain pathology in obese OLETF rats.

Carlos J Rodriguez-Ortiz, Max A Thorwald, Ruben Rodriguez, Marina Mejias-Ortega, Zanett Kieu, Neilabjo Maitra, Charlesice Hawkins, Joanna Valenzuela, Marcus Peng, Akira Nishiyama and 2 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical and experimental pharmacology & physiology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.7field-weighted citation impact, top 31% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 9 citations in OpenAlex.

  1. Review
  2. Review
  3. Neuroimmunology of Cardiovascular Disease.Current hypertension reports · 2024
    Review
  4. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 3 institutions in 3 countries.

Carlos J Rodriguez-OrtizCenter for Occupational and Environmental Health, Department of Environmental and Occupational Health, Department of Medicine, University of California, Irvine, California, USA.
Max A ThorwaldDepartment of Molecular and Cell Biology, University of California, Merced, California, USA.
Ruben RodriguezDepartment of Molecular and Cell Biology, University of California, Merced, California, USA.
Marina Mejias-OrtegaCenter for Occupational and Environmental Health, Department of Environmental and Occupational Health, Department of Medicine, University of California, Irvine, California, USA.
Zanett KieuDepartment of Molecular and Cell Biology, University of California, Merced, California, USA.
Neilabjo MaitraCenter for Occupational and Environmental Health, Department of Environmental and Occupational Health, Department of Medicine, University of California, Irvine, California, USA.
Charlesice HawkinsDepartment of Molecular and Cell Biology, University of California, Merced, California, USA.
Joanna ValenzuelaDepartment of Molecular and Cell Biology, University of California, Merced, California, USA.
Marcus PengCenter for Occupational and Environmental Health, Department of Environmental and Occupational Health, Department of Medicine, University of California, Irvine, California, USA.
Akira NishiyamaDepartment of Pharmacology, Kagawa Medical University, Kagawa, Japan.
Rudy M OrtizDepartment of Molecular and Cell Biology, University of California, Merced, California, USA.ORCID 0000-0003-3715-7194
Masashi KitazawaCenter for Occupational and Environmental Health, Department of Environmental and Occupational Health, Department of Medicine, University of California, Irvine, California, USA.
University of California, Merced · USUniversity of Occupational and Environmental Health Japan · JPKagawa University · JP

Funding

UCSC MHIRT Research Training GrantT37MD001480 · NIMHD · UNIVERSITY OF CALIFORNIA SANTA CRUZ · PI ORTIZ, CHARLES L · 2005 to 2018
$3.4M
Environmental copper exposure and its impact on microglial Abeta clearanceR01ES024331 · NIEHS · UNIVERSITY OF CALIFORNIA, MERCED · PI KITAZAWA, MASASHI · 2014 to 2018
$2.7M
Mechanisms of Oxidative Stress and Inflammation during Prolonged Fasting and SleeR01HL091767 · NHLBI · UNIVERSITY OF CALIFORNIA, MERCED · PI ORTIZ, RUDY M · 2009 to 2013
$1.9M
NHLBI NIH HHS R01 HL091767NIEHS NIH HHS R01 ES024331NIMHD NIH HHS T37 MD001480
6 · The paper itself

Abstract

Metabolic syndrome (MetS) is a rapidly increasing health concern during midlife and is an emerging risk factor for the development of neurodegenerative diseases, such as Alzheimer's disease (AD). While angiotensin receptor blockers (ARB) are widely used for MetS-associated hypertension and kidney disease, its therapeutic potential in the brain during MetS are not well-described. Here, we tested whether treatment with ARB could alleviate the brain pathology and inflammation associated with MetS using the Otsuka Long-Evans Tokushima Fatty (OLETF) rat. Here, we report that chronic ARB treatment with olmesartan (10 mg/kg/day by oral gavage for 6 weeks) partially but significantly ameliorated accumulation of oxidized and ubiquitinated proteins, astrogliosis and transformation to neurotoxic astrocytes in the brain of old OLETF rats, which otherwise exhibit the progression of these pathological hallmarks associated with MetS. Additionally, olmesartan treatment restored claudin-5 and ZO-1, markers of the structural integrity of the blood-brain barrier as well as synaptic protein PSD-95, which were otherwise decreased in old OLETF rats, particularly in the hippocampus, a critical region in cognition, memory and AD. These data demonstrate that the progression of MetS in OLETF rats is associated with deterioration of various aspects of neuronal integrity that may manifest neurodegenerative conditions and that overactivation of angiotensin receptor directly or indirectly contributes to these detriments. Thus, olmesartan treatment may slow or delay the onset of degenerative process in the brain and subsequent neurological disorders associated with MetS.

Indexed as

Diabetes Mellitus, Type 2Metabolic SyndromeAngiotensin-Converting Enzyme InhibitorsAngiotensin Receptor AntagonistsAnimalsBlood GlucoseBrainImidazolesObesityRatsRats, Inbred OLETFRats, Long-EvansReceptors, AngiotensinTetrazolesAngiotensin-Converting Enzyme InhibitorsAngiotensin Receptor AntagonistsBlood GlucoseImidazolesolmesartanReceptors, AngiotensinTetrazolesblood-brain barriercerebrovasculaturegliosishippocampusneurodegenerationsynapse

Identifiers

PMID36398458
PMCPMC9898104
OpenAlexW4309360435

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.