Evidence map›Paper›PMID 40494844›Full record

ArticleTranslational psychiatry2025

Exploring individual differences in fear extinction in male and female mice: insights from HPA axis, microbiota, and transcriptomics.

Marc Ten-Blanco, María Ponce-Renilla, Inmaculada Pereda-Pérez, Cristina Izquierdo-Luengo, Carlo Bressa, Olga Zafra, Rosa María Tolón, Fernando Berrendero

Abstract read
In one paragraph

Article in Translational psychiatry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0cells of the map it votes in
0citing papers in PubMed
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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

8 authors.

Marc Ten-Blanco *Neurobiology of Addictive Disorders and Anxiety Research Group, Institute of Life Sciences, Faculty of Experimental Sciences, Universidad Francisco de Vitoria, 28223, Pozuelo de Alarcón, Madrid, Spain.
María Ponce-Renilla *Neurobiology of Addictive Disorders and Anxiety Research Group, Institute of Life Sciences, Faculty of Experimental Sciences, Universidad Francisco de Vitoria, 28223, Pozuelo de Alarcón, Madrid, Spain.
Inmaculada Pereda-PérezNeurobiology of Addictive Disorders and Anxiety Research Group, Institute of Life Sciences, Faculty of Experimental Sciences, Universidad Francisco de Vitoria, 28223, Pozuelo de Alarcón, Madrid, Spain.
Cristina Izquierdo-LuengoNeurobiology of Addictive Disorders and Anxiety Research Group, Institute of Life Sciences, Faculty of Experimental Sciences, Universidad Francisco de Vitoria, 28223, Pozuelo de Alarcón, Madrid, Spain.ORCID http://orcid.org/0000-0001-7079-5054
Carlo BressaMicrobial Biotechnology Research Group, Institute of Life Sciences, Faculty of Experimental Sciences, Universidad Francisco de Vitoria, 28223, Pozuelo de Alarcón, Madrid, Spain.ORCID http://orcid.org/0000-0001-5530-4958
Olga ZafraMicrobial Biotechnology Research Group, Institute of Life Sciences, Faculty of Experimental Sciences, Universidad Francisco de Vitoria, 28223, Pozuelo de Alarcón, Madrid, Spain.ORCID http://orcid.org/0000-0002-2379-3184
Rosa María TolónNeurobiology of Addictive Disorders and Anxiety Research Group, Institute of Life Sciences, Faculty of Experimental Sciences, Universidad Francisco de Vitoria, 28223, Pozuelo de Alarcón, Madrid, Spain.
Fernando BerrenderoNeurobiology of Addictive Disorders and Anxiety Research Group, Institute of Life Sciences, Faculty of Experimental Sciences, Universidad Francisco de Vitoria, 28223, Pozuelo de Alarcón, Madrid, Spain. fernando.berrendero@ufv.es.ORCID http://orcid.org/0000-0003-3502-9439

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Exposure to traumatic life events may compromise physical and mental health of specific subjects. While some individuals extinguish fear appropriately, others exhibit an inefficient and persistent fear response, with remarkable differences between sexes. Understanding the heterogeneity in fear extinction responses is essential for elucidating the underlying mechanisms of fear-related disorders. We used a multidisciplinary approach analyzing the hypothalamic-pituitary-adrenal (HPA) axis tone, the microbiota composition, and the transcriptome of the amygdala (primary brain region involved in fear regulation) in adult male and female mice that were exposed to the Pavlovian fear conditioning and extinction paradigm. This model allowed us to stratify the mice population into two extreme phenotypic subgroups (resilient and susceptible), based on their individual fear extinction behavior. Characterization of some components of the HPA axis revealed strong disturbances in vulnerable males (e.g., increased hypothalamic CRF mRNA and corticosterone plasma levels), whereas softer changes were found in female animals. Several bacterial groups such as the genera Parvibacter, Alloprevotella and Limosilactobacillus and the family Christensenellaceae were enriched in the microbiota of resilient males, as well as relevant bacterial taxa enrichment was also observed in resilient (genus Muribaculum) and susceptible (family Eggerthellaceae) female mice. We also identified clear differences in the transcriptomic profile of the amygdala (31 differentially expressed genes) in male animals. These findings underscore the intricate involvement of multiple factors shaping the inter-individual variability of fear extinction response in a sex-dependent manner, thus paving the way for new potential targets for fear-related disorders.

Indexed as

AmygdalaExtinction, PsychologicalFearHypothalamo-Hypophyseal SystemIndividualityMicrobiotaPituitary-Adrenal SystemTranscriptomeAnimalsBehavior, AnimalConditioning, ClassicalCorticosteroneFemaleMaleMiceMice, Inbred C57BLCorticosterone

Identifiers

PMID40494844
PMCPMC12152170

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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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 Socratic graph.