Evidence map›Paper›PMID 31813125›Full record

ArticleMolecular neurobiology2020

Extracellular Vesicles in the Forebrain Display Reduced miR-346 and miR-331-3p in a Rat Model of Chronic Temporal Lobe Epilepsy.

Daniel Leite Góes Gitaí, Ygor Daniel Ramos Dos Santos, Raghavendra Upadhya, Maheedhar Kodali, Leelavathi N Madhu, Ashok K Shetty

Open access · greenAbstract read
In one paragraph

Article in Molecular neurobiology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
1.0field-weighted citation impact, top 28% 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

23 citing papers in PubMed, 28 citations in OpenAlex.

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  16. Function of exosomes in neurological disorders and brain tumors.Extracellular vesicles and circulating nucleic acids · 2021
    Article
  17. Article
  18. The Role of GM130 in Nervous System Diseases.Frontiers in neurology · 2021
    Review
  19. Article
  20. 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 3 institutions in 2 countries.

Daniel Leite Góes GitaíInstitute for Regenerative Medicine, Department of Molecular and Cellular Medicine, Texas A&M University Health Science Center College of Medicine, 1114 TAMU, 206 Olsen Boulevard, College Station, TX, 77843, USA. daniel.gitai@icbs.ufal.com.
Ygor Daniel Ramos Dos SantosInstitute of Biological Sciences and Health, Federal University of Alagoas, Av. Lourival Melo Mota, S/N Tabuleiro do Martins, Maceió, AL, 57072-900, Brazil.
Raghavendra UpadhyaInstitute for Regenerative Medicine, Department of Molecular and Cellular Medicine, Texas A&M University Health Science Center College of Medicine, 1114 TAMU, 206 Olsen Boulevard, College Station, TX, 77843, USA.
Maheedhar KodaliInstitute for Regenerative Medicine, Department of Molecular and Cellular Medicine, Texas A&M University Health Science Center College of Medicine, 1114 TAMU, 206 Olsen Boulevard, College Station, TX, 77843, USA.
Leelavathi N MadhuInstitute for Regenerative Medicine, Department of Molecular and Cellular Medicine, Texas A&M University Health Science Center College of Medicine, 1114 TAMU, 206 Olsen Boulevard, College Station, TX, 77843, USA.
Ashok K ShettyInstitute for Regenerative Medicine, Department of Molecular and Cellular Medicine, Texas A&M University Health Science Center College of Medicine, 1114 TAMU, 206 Olsen Boulevard, College Station, TX, 77843, USA. shetty@medicine.tamhsc.edu.ORCID http://orcid.org/0000-0001-5049-6671
Texas A&M Health Science Center · USTexas A&M Health Science Center · USUniversidade Federal de Alagoas · BR

Funding

Mesenchymal Stem Cell Derived Extracellular Vesicles for Traumatic Brain InjuryR01NS106907 · NINDS · TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR · PI ASHOK K SHETTY · 2018 to 2026
$4.0M
Combined NSC Grafting and Neurogenic Drug Therapy for Temporal Lobe EpilepsyI01BX002351 · VA · OLIN TEAGUE VETERANS CENTER · PI SHETTY, ASHOK K · 2015 to 2018
–
BLR&D Research Career Scientist AwardIK6BX003612 · VA · OLIN TEAGUE VETERANS CENTER · PI SHETTY, ASHOK K · 2017 to 2019
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BLRD VA I01 BX000883BLRD VA I01 BX002351BLRD VA IK6 BX003612NINDS NIH HHS R01 NS106907Texas Emerging Technology Fund No numberU.S. Department of Defense W81XWH-14-1-0558U.S. Department of Veterans Affairs I01BX000883
6 · The paper itself

Abstract

An initial precipitating injury in the brain, such as after status epilepticus (SE), evolves into chronic temporal lobe epilepsy (TLE). We investigated changes in the miRNA composition of extracellular vesicles (EVs) in the forebrain after the establishment of SE-induced chronic TLE. We induced SE in young Fischer 344 rats through graded intraperitoneal injections of kainic acid, which resulted in consistent spontaneous recurrent seizures at ~ 3 months post-SE. We isolated EVs from the entire forebrain of chronically epileptic rats and age-matched naïve control animals through an ultracentrifugation method and performed miRNA-sequencing studies to discern changes in the miRNA composition of forebrain-derived EVs in chronic epilepsy. EVs from both naïve and epileptic forebrains displayed spherical or cup-shaped morphology, a comparable size range, and CD63 expression but lacked the expression of a deep cellular marker GM130. However, miRNA-sequencing studies suggested downregulation of 3 miRNAs (miR-187-5p, miR-346, and miR-331-3p) and upregulation of 4 miRNAs (miR-490-5p, miR-376b-3p, miR-493-5p, and miR-124-5p) in EVs from epileptic forebrains with fold changes ranging from 1.5 to 2.4 (p < 0.0006; FDR < 0.05). By using geNorm and Normfinder software, we identified miR-487 and miR-221 as the best combination of reference genes for measurement of altered miRNAs found in the epileptic forebrain through qRT-PCR studies. The validation revealed that only miR-346 and miR-331-3p were significantly downregulated in EVs from the epileptic forebrain. The enrichment pathway analysis of these miRNAs showed an overrepresentation of signaling pathways that are linked to molecular mechanisms underlying chronic epilepsy, including GABA-ergic (miR-346 targets) and mTOR (miR-331-3p targets) systems. Thus, the packaging of two miRNAs into EVs in neural cells is considerably altered in chronic epilepsy. Functional studies on these two miRNAs may uncover their role in the pathophysiology and treatment of TLE.

Indexed as

AnimalsDisease Models, AnimalEpilepsy, Temporal LobeExtracellular VesiclesMaleMicroRNAsNeuronsRats, Inbred F344Status EpilepticusMicroRNAsEpilepsyEpileptogenesisExosomesExtracellular vesiclesMicroRNAsmTOR signaling pathwaySeizuresTemporal lobe epilepsy

Identifiers

PMID31813125
PMCPMC8011947
OpenAlexW2992140359

What OpenQuestion holds

Textmetadata
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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.