Evidence map›Paper›PMID 29410441›Full record

ArticleScientific reports2018

Involvement of PKA/DARPP-32/PP1α and β- arrestin/Akt/GSK-3β Signaling in Cadmium-Induced DA-D2 Receptor-Mediated Motor Dysfunctions: Protective Role of Quercetin.

Richa Gupta, Rajendra K Shukla, Ankita Pandey, Tanuj Sharma, Yogesh K Dhuriya, Pranay Srivastava, Manjul P Singh, Mohammad Imran Siddiqi, Aditya B Pant, Vinay K Khanna

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.8field-weighted citation impact, top 18% 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

11 citing papers in PubMed, 36 citations in OpenAlex.

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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

10 authors at 3 institutions in 1 country.

Richa GuptaDevelopmental Toxicology Laboratory, Systems Toxicology and Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research, Vishvigyan Bhawan, 31 Mahatma Gandhi Marg, Lucknow, 226 001, Uttar Pradesh, India.
Rajendra K ShuklaDevelopmental Toxicology Laboratory, Systems Toxicology and Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research, Vishvigyan Bhawan, 31 Mahatma Gandhi Marg, Lucknow, 226 001, Uttar Pradesh, India.
Ankita PandeyDevelopmental Toxicology Laboratory, Systems Toxicology and Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research, Vishvigyan Bhawan, 31 Mahatma Gandhi Marg, Lucknow, 226 001, Uttar Pradesh, India.
Tanuj SharmaMolecular and Structural Biology, CSIR-Central Drug Research Institute, Sitapur Road, Sector 10, Jankipuram Extension, Lucknow, 226 031, Uttar Pradesh, India.
Yogesh K DhuriyaDevelopmental Toxicology Laboratory, Systems Toxicology and Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research, Vishvigyan Bhawan, 31 Mahatma Gandhi Marg, Lucknow, 226 001, Uttar Pradesh, India.
Pranay SrivastavaDevelopmental Toxicology Laboratory, Systems Toxicology and Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research, Vishvigyan Bhawan, 31 Mahatma Gandhi Marg, Lucknow, 226 001, Uttar Pradesh, India.ORCID 0000-0002-9289-2696
Manjul P SinghSchool of Pharmacy, Babu Banarsi Das University, Faizabad Road, Lucknow, 226 028, Uttar Pradesh, India.
Mohammad Imran SiddiqiMolecular and Structural Biology, CSIR-Central Drug Research Institute, Sitapur Road, Sector 10, Jankipuram Extension, Lucknow, 226 031, Uttar Pradesh, India.
Aditya B PantDevelopmental Toxicology Laboratory, Systems Toxicology and Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research, Vishvigyan Bhawan, 31 Mahatma Gandhi Marg, Lucknow, 226 001, Uttar Pradesh, India.
Vinay K KhannaDevelopmental Toxicology Laboratory, Systems Toxicology and Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research, Vishvigyan Bhawan, 31 Mahatma Gandhi Marg, Lucknow, 226 001, Uttar Pradesh, India. vkkhanna1@rediffmail.com.
Indian Institute of Toxicology Research · INBabu Banarasi Das University · INCentral Drug Research Institute · IN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Given increasing risk of cadmium-induced neurotoxicity, the study was conducted to delineate the molecular mechanisms associated with cadmium-induced motor dysfunctions and identify targets that govern dopaminergic signaling in the brain involving in vivo, in vitro, and in silico approaches. Selective decrease in dopamine (DA)-D2 receptors on cadmium exposure was evident which affected the post-synaptic PKA/DARPP-32/PP1α and β-arrestin/Akt/GSK-3β signaling concurrently in rat corpus striatum and PC12 cells. Pharmacological inhibition of PKA and Akt in vitro demonstrates that both pathways are independently modulated by DA-D2 receptors and associated with cadmium-induced motor deficits. Ultrastructural changes in the corpus striatum demonstrated neuronal degeneration and loss of synapse on cadmium exposure. Further, molecular docking provided interesting evidence that decrease in DA-D2 receptors may be due to direct binding of cadmium at the competitive site of dopamine on DA-D2 receptors. Treatment with quercetin resulted in the alleviation of cadmium-induced behavioral and neurochemical alterations. This is the first report demonstrating that cadmium-induced motor deficits are associated with alteration in postsynaptic dopaminergic signaling due to a decrease in DA-D2 receptors in the corpus striatum. The results further demonstrate that quercetin has the potential to alleviate cadmium-induced dopaminergic dysfunctions.

Indexed as

Movement DisordersAnimalsAntioxidantsbeta-ArrestinsCadmiumCorpus StriatumCyclic AMP-Dependent Protein KinasesDopamineDopamine and cAMP-Regulated Phosphoprotein 32Glycogen Synthase Kinase 3 betaMalePC12 CellsProtein Phosphatase 1Proto-Oncogene Proteins c-aktQuercetinRatsAntioxidantsbeta-ArrestinsCadmiumCyclic AMP-Dependent Protein KinasesDopamineDopamine and cAMP-Regulated Phosphoprotein 32Glycogen Synthase Kinase 3 betaPpp1r1b protein, ratProtein Phosphatase 1Proto-Oncogene Proteins c-aktQuercetinReceptors, Dopamine D2

Identifiers

PMID29410441
PMCPMC5802731
OpenAlexW2806772373

What OpenQuestion holds

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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.