Evidence map›Paper›PMID 36688960›Full record

ArticleJournal of molecular medicine (Berlin, Germany)2023

Inhibition of ERK/CREB signaling contributes to postoperative learning and memory dysfunction in neonatal rats.

Hui Wang, Gang Ma, Jia Min, Jun Li, Weiran Shan, Zhiyi Zuo

Open access · greenAbstract read
In one paragraph

Article in Journal of molecular medicine (Berlin, Germany), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
2.0field-weighted citation impact, top 15% 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

5 citing papers in PubMed, 10 citations in OpenAlex.

  1. Article
  2. Review
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  4. Article
  5. 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

6 authors at 4 institutions in 2 countries.

Hui WangDepartment of Anesthesiology, University of Virginia, Charlottesville, VA, 22901, USA.
Gang MaDepartment of Anesthesiology, University of Virginia, Charlottesville, VA, 22901, USA.
Jia MinDepartment of Anesthesiology, University of Virginia, Charlottesville, VA, 22901, USA.
Jun LiDepartment of Anesthesiology, University of Virginia, Charlottesville, VA, 22901, USA.
Weiran ShanDepartment of Anesthesiology, University of Virginia, Charlottesville, VA, 22901, USA.
Zhiyi ZuoDepartment of Anesthesiology, University of Virginia, Charlottesville, VA, 22901, USA. zz3c@virginia.edu.ORCID 0000-0002-3542-5047
Ningxia Medical University · CNUniversity of Virginia · USNanchang University · CNUniversity of Virginia Hospital · US

Funding

Role of carboxyl-terminal modulator protein in autophagy and senescence of human induced pluripotent stem cellsRF1AG061047 · NIA · UNIVERSITY OF VIRGINIA · PI WENKER, IAN CHRISTOPHER · 2019 to 2023
$2.4M
Obesity-induced cerebral vascular remodeling and poor brain ischemic toleranceR01NS099118 · NINDS · UNIVERSITY OF VIRGINIA · PI ZUO, ZHIYI · 2018 to 2022
$1.7M
Glial cell line-derived neurotropic factor and postoperative cognitive impairment in young ratsR01HD089999 · NICHD · UNIVERSITY OF VIRGINIA · PI ZUO, ZHIYI · 2017 to 2021
$1.7M
NIA NIH HHS RF1 AG061047NICHD NIH HHS R01 HD089999NIH HHS R01 HD089999NINDS NIH HHS R01 NS099118
6 · The paper itself

Abstract

Exposure to surgery with anesthesia early in life may lead to abnormal behavior, learning, and memory in humans. Pre-clinical studies have suggested a critical role of glial cell-derived neurotrophic factor (GDNF) in these effects. We hypothesize that the inhibition of extracellular signal-regulated kinase (ERK)-cAMP response element-binding protein (CREB) pathway contributes to GDNF decrease and the dysfunction of learning and memory. To address this hypothesis, 7-day-old Sprague-Dawley male and female rats were subjected to right carotid artery exposure (surgery) under sevoflurane anesthesia. Their learning and memory were tested by the Barnes maze, and novel object recognition tests started 23 days after the surgery. Blood and brain were harvested at various times after surgery for biochemical analyses. Rats with surgery and anesthesia performed poorly in the Barnes maze and novel object recognition tests compared with control rats. Rats with surgery had a decreased GDNF concentration in the brain and urine. The concentrations of urine GDNF were negatively correlated with the performance of rats in a delayed memory phase of the Barnes maze test. Surgery increased proinflammatory cytokines in the blood and brain. Intracerebroventricular injection of GDNF attenuated the increased inflammatory response in surgery rats. Surgery inhibited ERK and CREB. Inhibiting ERK reduced GDNF and induced poor performance in the Barnes maze and novel object recognition tests of rats without surgery. Surgery also increased brain-derived natriuretic peptide (BNP) in the brain. Intracerebroventricular injection of BNP inhibited ERK and CREB, reduced GDNF, and impaired learning and memory. Surgery, ERK inhibition, and BNP reduced the expression of synaptic proteins. Our results suggest that surgery increases BNP that inhibits ERK-CREB signaling to reduce GDNF, which leads to an unbalanced inflammatory response and a reduced synaptic protein expression for the development of postoperative cognitive dysfunction. KEY MESSAGES: Surgery increases BNP and decreases ERK/CREB signaling to reduce GDNF. The increase in BNP and decrease in ERK/CREB signaling contribute to postoperative cognitive dysfunction. GDNF reduction contributes to neuroinflammatory response after surgery. Urine GDNF concentrations are negatively corrected with poor spatial memory performance.

Indexed as

Extracellular Signal-Regulated MAP KinasesPostoperative Cognitive ComplicationsAnimalsAnimals, NewbornCyclic AMP Response Element-Binding ProteinFemaleGlial Cell Line-Derived Neurotrophic FactorHippocampusHumansMaleMaze LearningMemory DisordersRatsRats, Sprague-DawleyCreb1 protein, ratCyclic AMP Response Element-Binding ProteinExtracellular Signal-Regulated MAP KinasesGlial Cell Line-Derived Neurotrophic FactorExtracellular signal-regulated kinaseGlial cell-derived neurotrophic factorNeuroinflammationPostoperative cognitive dysfunctionRats

Identifiers

PMID36688960
PMCPMC10676212
OpenAlexW4317780527

What OpenQuestion holds

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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 OpenQuestion graph.