Evidence map›Paper›PMID 19357782›Full record

ArticlePloS one2009

Beneficial effects of estrogen in a mouse model of cerebrovascular insufficiency.

Naohito Kitamura, Runa Araya, Moeko Kudoh, Haruo Kishida, Tetsuya Kimura, Miyuki Murayama, Akihiko Takashima, Yuriko Sakamaki, Tsutomu Hashikawa, Shingo Ito and 4 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
3.2field-weighted citation impact, top 10% 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

14 citing papers in PubMed, 35 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Lisdexamfetamine Effects on Executive Activation and Neurochemistry in Menopausal Women with Executive Function Difficulties.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2017
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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

14 authors at 3 institutions in 2 countries.

Naohito KitamuraYamada Research Unit, RIKEN Brain Science Institute, Saitama, Japan.
Runa Araya
Moeko Kudoh
Haruo Kishida
Tetsuya Kimura
Miyuki Murayama
Akihiko Takashima
Yuriko Sakamaki
Tsutomu Hashikawa
Shingo Ito
Sumio Ohtsuki
Tetsuya Terasaki
Jürgen Wess
Masahisa Yamada
RIKEN Center for Brain Science · JPTohoku University · JPNational Institute of Diabetes and Digestive and Kidney Diseases · US

Funding

Muscarinic acetylcholine receptor subtypes: physiological rolesZIADK075020 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI WESS, JURGEN · 2009 to 2025
$6.1M
6 · The paper itself

Abstract

backgroundThe M(5) muscarinic acetylcholine receptor is known to play a crucial role in mediating acetylcholine dependent dilation of cerebral blood vessels. Previously, we reported that male M(5) muscarinic acetylcholine knockout mice (M5R(-/-) mice) suffer from a constitutive constriction of cerebral arteries, reduced cerebral blood flow, dendritic atrophy, and short-term memory loss, without necrosis and/or inflammation in the brain. METHODOLOGY/PRINCIPAL

findingsWe employed the Magnetic Resonance Angiography to study the area of the basilar artery in male and female M5R(-/-) mice. Here we show that female M5R(-/-) mice did not show the reduction in vascular area observed in male M5R(-/-) mice. However, ovariectomized female M5R(-/-) mice displayed phenotypic changes similar to male M5R(-/-) mice, strongly suggesting that estrogen plays a key role in the observed gender differences. We found that 17beta-estradiol (E2) induced nitric oxide release and ERK activation in a conditional immortalized mouse brain cerebrovascular endothelial cell line. Agonists of ERalpha, ERbeta, and GPR30 promoted ERK activation in this cell line. Moreover, in vivo magnetic resonance imaging studies showed that the cross section of the basilar artery was restored to normal in male M5R(-/-) mice treated with E2. Treatment with E2 also improved the performance of male M5R(-/-) mice in a cognitive test and reduced the atrophy of neural dendrites in the cerebral cortex and hippocampus. M5R(-/-) mice also showed astrocyte swelling in cortex and hippocampus using the three-dimensional reconstruction of electron microscope images. This phenotype was reversed by E2 treatment, similar to the observed deficits in dendrite morphology and the number of synapses. CONCLUSIONS/SIGNIFICANCE: Our findings indicate that M5R(-/-) mice represent an excellent novel model system to study the beneficial effects of estrogen on cerebrovascular function and cognition. E2 may offer new therapeutic perspectives for the treatment of cerebrovascular insufficiency related memory dysfunction.

Indexed as

Cerebrovascular DisordersDisease Models, AnimalEstrogensAnimalsBasilar ArteryBethanecholBrainCell LineCerebrovascular CirculationCognitionEnzyme ActivationExtracellular Signal-Regulated MAP KinasesFemaleHumansMagnetic Resonance AngiographyMaleBethanecholEstrogensExtracellular Signal-Regulated MAP KinasesGPER1 protein, mouseMuscarinic AgonistsNitric OxideReceptor, Muscarinic M5Receptors, EstrogenReceptors, G-Protein-CoupledSodium-Hydrogen Exchangers

Identifiers

PMID19357782
PMCPMC2664330
OpenAlexW1977008074

What OpenQuestion holds

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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 OpenQuestion graph.