Evidence map›Paper›PMID 38715397›Full record

ArticleBrain and behavior2024

Role of the prefrontal cortical protease TACE/ADAM17 in neurobehavioral responses to chronic stress during adolescence.

Fransua Sharafeddin, Julio Sierra, Mina Ghaly, Timothy B Simon, Perla Ontiveros-Ángel, Brandon Edelbach, Marcelo Febo, Jennifer Labus, Johnny D Figueroa

Abstract read
In one paragraph

Article in Brain and behavior, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

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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

9 authors.

Fransua SharafeddinCenter for Health Disparities and Molecular Medicine, Loma Linda University School of Medicine, Loma Linda, California, USA.
Julio SierraCenter for Health Disparities and Molecular Medicine, Loma Linda University School of Medicine, Loma Linda, California, USA.ORCID 0000-0003-3261-777X
Mina GhalyCenter for Health Disparities and Molecular Medicine, Loma Linda University School of Medicine, Loma Linda, California, USA.
Timothy B SimonCenter for Health Disparities and Molecular Medicine, Loma Linda University School of Medicine, Loma Linda, California, USA.
Perla Ontiveros-ÁngelCenter for Health Disparities and Molecular Medicine, Loma Linda University School of Medicine, Loma Linda, California, USA.
Brandon EdelbachDepartment of Neurosurgery, Loma Linda University School of Medicine Loma Linda, CA, USA.
Marcelo FeboTranslational Research Imaging Laboratory, Department of Psychiatry, Department of Neuroscience, College of Medicine, University of Florida Health, Gainesville, Florida, USA.ORCID 0000-0001-8981-4163
Jennifer LabusGraduate Program in Bioscience, Division of Digestive Diseases, David Geffen School of Medicine, University of California, Los Angeles, USA.
Johnny D FigueroaCenter for Health Disparities and Molecular Medicine, Loma Linda University School of Medicine, Loma Linda, California, USA.ORCID 0000-0003-4769-8736

Funding

NIH-LLU Initiative for Maximizing Student DiversityR25GM060507 · NIGMS · LOMA LINDA UNIVERSITY · PI DE LEON, MARINO · 2001 to 2022
$11.3M
Research Training/Education CoreP20MD006988 · NIMHD · LOMA LINDA UNIVERSITY · PI DE LEON, MARINO · 2012 to 2016
$6.2M
NEUROPATHOLOGICAL SIGNATURES CONNECTING EARLY-LIFE TRAUMA TO COMPULSIVE EATING BEHAVIOR AND OBESITYR21DK124727 · NIDDK · LOMA LINDA UNIVERSITY · PI FIGUEROA, JOHNNY DAVIS · 2020 to 2022
$753k
NIDDK NIH HHS R21 DK124727NIGMS NIH HHS R25 GM060507NIH HHS DK124727NIH HHS GM060507NIH HHS MD006988NIMHD NIH HHS P20 MD006988
6 · The paper itself

Abstract

introductionChronic adolescent stress profoundly affects prefrontal cortical networks regulating top-down behavior control. However, the neurobiological pathways contributing to stress-induced alterations in the brain and behavior remain largely unknown. Chronic stress influences brain growth factors and immune responses, which may, in turn, disrupt the maturation and function of prefrontal cortical networks. The tumor necrosis factor alpha-converting enzyme/a disintegrin and metalloproteinase 17 (TACE/ADAM17) is a sheddase with essential functions in brain maturation, behavior, and inflammatory responses. This study aimed to determine the impact of stress on the prefrontal cortex and whether TACE/ADAM17 plays a role in these responses.

methodsWe used a Lewis rat model that incorporates critical elements of chronic psychosocial stress, such as uncontrollability, unpredictability, lack of social support, and re-experiencing of trauma.

resultsChronic stress during adolescence reduced the acoustic startle reflex and social interactions while increasing extracellular free water content and TACE/ADAM17 mRNA levels in the medial prefrontal cortex. Chronic stress altered various ethological behavioral domains in the observation home cages (decreased ingestive behaviors and increased walking, grooming, and rearing behaviors). A group of rats was injected intracerebrally either with a novel Accell™ SMARTpool TACE/ADAM17 siRNA or a corresponding siRNA vehicle (control). The RNAscope Multiplex Fluorescent v2 Assay was used to visualize mRNA expression. Automated puncta quantification and analyses demonstrated that TACE/ADAM17 siRNA administration reduced TACE/ADAM17 mRNA levels in the medial prefrontal cortex (59% reduction relative to control). We found that the rats that received prefrontal cortical TACE/ADAM17 siRNA administration exhibited altered eating patterns (e.g., increased food intake and time in the feeding zone during the light cycle).

conclusionThis study supports that the prefrontal cortex is sensitive to adolescent chronic stress and suggests that TACE/ADAM17 may be involved in the brain responses to stress.

Indexed as

ADAM17 ProteinPrefrontal CortexRats, Inbred LewStress, PsychologicalAnimalsBehavior, AnimalFemaleMaleRatsReflex, StartleADAM17 ProteinAdam17 protein, ratchronic adolescent stresshome‐cage monitoringnaturalistic behaviorsprefrontal cortexRNA silencing

Identifiers

PMID38715397
PMCPMC11077197

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Registered trials

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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.