Evidence map›Paper›PMID 40520207›Full record

ArticleFrontiers in pharmacology2025

Prenatal modulation of NADPH-oxidase reverses the deranged GABA switch and rescues behavioral deficits in valproate ASD rat model.

Basma A Yasseen, Hadeer Abdelkhalek, Sara Gohar, Yasmin Hatem, Hajar El-Sayed, Aya A Elkhodiry, Aya Galal, Aya Samir, Nouran Al-Shehaby, Malak W Elbenhawi and 10 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Frontiers in pharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. 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

20 authors.

Basma A YasseenTumor Biology Research Program, Research Department, Children's Cancer Hospital Egypt, Cairo, Egypt.
Hadeer AbdelkhalekTumor Biology Research Program, Research Department, Children's Cancer Hospital Egypt, Cairo, Egypt.
Sara GoharTumor Biology Research Program, Research Department, Children's Cancer Hospital Egypt, Cairo, Egypt.
Yasmin HatemTumor Biology Research Program, Research Department, Children's Cancer Hospital Egypt, Cairo, Egypt.
Hajar El-SayedTumor Biology Research Program, Research Department, Children's Cancer Hospital Egypt, Cairo, Egypt.
Aya A ElkhodiryTumor Biology Research Program, Research Department, Children's Cancer Hospital Egypt, Cairo, Egypt.
Aya GalalPreclinical and Translational Research Center, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
Aya SamirTumor Biology Research Program, Research Department, Children's Cancer Hospital Egypt, Cairo, Egypt.
Nouran Al-ShehabyTumor Biology Research Program, Research Department, Children's Cancer Hospital Egypt, Cairo, Egypt.
Malak W ElbenhawiTumor Biology Research Program, Research Department, Children's Cancer Hospital Egypt, Cairo, Egypt.
Rehab HamdyTumor Biology Research Program, Research Department, Children's Cancer Hospital Egypt, Cairo, Egypt.
Christine S PrinceTumor Biology Research Program, Research Department, Children's Cancer Hospital Egypt, Cairo, Egypt.
Azza G KamelTumor Biology Research Program, Research Department, Children's Cancer Hospital Egypt, Cairo, Egypt.
Mohamed A BadawyTumor Biology Research Program, Research Department, Children's Cancer Hospital Egypt, Cairo, Egypt.
Ghada F SolimanDepartment of Medical Pharmacology, Faculty of Medicine, Cairo University, Cairo, Egypt.
Soha Aly ElMorsyDepartment of Medical Pharmacology, Faculty of Medicine, Cairo University, Cairo, Egypt.
Tamer M Gamal El-DinDepartment of Pharmacology, University of Washington, Seattle, WA, United States.
Ebtehal El-DemerdashPreclinical and Translational Research Center, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
Sameh S AliTumor Biology Research Program, Research Department, Children's Cancer Hospital Egypt, Cairo, Egypt.
Engy A Abdel-RahmanTumor Biology Research Program, Research Department, Children's Cancer Hospital Egypt, Cairo, Egypt.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Indroduction: Impaired depolarizing-to-hyperpolarizing (D/H) switch of gamma-aminobutyric acid (GABA) is reported during brain development in rodent valproate-model of autism spectrum disorder (VPA-ASD). We hypothesize that this impairment triggers NADPH oxidases (NOXs)-induced reactive oxygen species (ROS) overproduction. Methods: Here, we followed the impact of prenatal exposure to VPA on the synaptic protein expression of potassium chloride cotransporter 2 (KCC2), sodium potassium chloride cotransporter 1 (NKCC1) and, in brains of male and female Wistar rats during infantile (P15), juvenile (P30) and adult (P60) stages. We also assessed alterations in synaptic NOX isoforms 2 and 4 (NOX2 and NOX4) activities and expressions in developing rat brains. Results: Our findings revealed a significant reduction in KCC2 expression and a concomitant increase in NOX activity and NOX4 expression in synaptosomes of VPA-exposed rats, particularly at P15 and P30. Prenatal exposure to shikonin, (10 mg/kg/day, intraperitoneal (i.p.) into pregnant dam, daily from G12.5 until birth), ameliorated these effects by reducing synaptic protein expression of NOX4, generally quenched synaptic NOX activity and enhanced synaptic protein expression of KCC2. Indeed, shikonin reversed VPA-induced sociability deficits in ASD rats. Discussion: These results suggest that targeting the NOX-ROS pathway may be a potential therapeutic strategy for ASD.

Indexed as

ASDGABA D/H switchKCC2NOXshikoninsynaptosomes

Identifiers

PMID40520207
PMCPMC12162577

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.