Evidence map›Paper›PMID 24184018›Full record

ArticleExperimental neurology2013

Endogenous PI3K/Akt and NMDAR act independently in the regulation of CREB activity in lumbosacral spinal cord in cystitis.

Jarren C Kay, Chun-Mei Xia, Miao Liu, Shanwei Shen, Sharon J Yu, Chulwon Chung, Li-Ya Qiao

Open access · greenAbstract read
In one paragraph

Article in Experimental neurology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
5.2field-weighted citation impact, top 5% 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

28 citing papers in PubMed, 43 citations in OpenAlex.

  1. Review
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  11. Spinal neuron-glia-immune interaction in cross-organ sensitization.American journal of physiology. Gastrointestinal and liver physiology · 2020
    Review
  12. BDNF as a Promising Therapeutic Agent in Parkinson's Disease.International journal of molecular sciences · 2020
    Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Effect of SQW on the bladder function of mice lacking TRPV1.BMC complementary and alternative medicine · 2016
    Article
  19. Article
  20. Article
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

7 authors at 1 institution in 1 country.

Jarren C Kay *Department of Physiology and Biophysics, Virginia Commonwealth University School of Medicine, Richmond, Virginia.
Chun-Mei Xia *Department of Physiology and Biophysics, Virginia Commonwealth University School of Medicine, Richmond, Virginia.
Miao LiuDepartment of Physiology and Biophysics, Virginia Commonwealth University School of Medicine, Richmond, Virginia.
Shanwei ShenDepartment of Physiology and Biophysics, Virginia Commonwealth University School of Medicine, Richmond, Virginia.
Sharon J YuDepartment of Physiology and Biophysics, Virginia Commonwealth University School of Medicine, Richmond, Virginia.
Chulwon ChungDepartment of Physiology and Biophysics, Virginia Commonwealth University School of Medicine, Richmond, Virginia.
Li-Ya QiaoDepartment of Physiology and Biophysics, Virginia Commonwealth University School of Medicine, Richmond, Virginia.
Virginia Commonwealth University · US

Funding

Neurotrophins and Neuropeptides in Colon and Bladder HypersensitivityR01DK077917 · NIDDK · VIRGINIA COMMONWEALTH UNIVERSITY · PI QIAO, LIYA · 2008 to 2016
$2.8M
NIDDK NIH HHS R01 DK077917
6 · The paper itself

Abstract

The integral interaction of signaling components in the regulation of visceral inflammation-induced central sensitization in the spinal cord has not been well studied. Here we report that phosphoinositide 3-kinase (PI3K)-dependent Akt activation and N-methyl-d-aspartic acid receptor (NMDAR) in lumbosacral spinal cord independently regulate the activation of cAMP response element-binding protein (CREB) in vivo in a rat visceral pain model of cystitis induced by intraperitoneal injection of cyclophosphamide (CYP). We demonstrate that suppression of endogenous PI3K/Akt activity with a potent PI3K inhibitor LY294002 reverses CYP-induced phosphorylation of CREB, however, it has no effect on CYP-induced phosphorylation of NR1 at Ser(897) and Ser(896); conversely, inhibition of NMDAR in vivo with MK801 fails to block CYP-induced Akt activation but significantly attenuates CYP-induced CREB phosphorylation in lumbosacral spinal cord. This novel interrelationship of PI3K/Akt, NMDAR, and CREB activation in lumbosacral spinal cord is further confirmed in an ex vivo spinal slice culture system exposed to an excitatory neurotransmitter calcitonin gene-related peptide (CGRP). Consistently we found that CGRP-triggered CREB activation can be blocked by both PI3K inhibitor LY294002 and NMDAR antagonists MK801 and D-AP5. However, CGRP-triggered Akt activation cannot be blocked by MK801 or D-AP5; vice versa, LY294002 pretreatment that suppresses the Akt activity fails to reverse CGRP-elicited NR1 phosphorylation. These results suggest that PI3K/Akt and NMDAR independently regulate spinal plasticity in visceral pain model, and target of a single pathway is necessary but not sufficient in treatment of visceral hypersensitivity.

Indexed as

AnimalsBlotting, WesternCentral Nervous System SensitizationCyclic AMP Response Element-Binding ProteinCystitisDisease Models, AnimalImmunohistochemistryLumbosacral RegionMalePhosphatidylinositol 3-KinasesPhosphorylationProto-Oncogene Proteins c-aktRatsRats, Sprague-DawleyReceptors, N-Methyl-D-AspartateSignal TransductionCyclic AMP Response Element-Binding ProteinPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktReceptors, N-Methyl-D-AspartateAktCentral sensitizationCREBNMDARSpinal cord

Identifiers

PMID24184018
PMCPMC3878196
OpenAlexW1993205491

What OpenQuestion 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 OpenQuestion graph.