Indirectly acquired fear memories have distinct, sex-specific molecular signatures from directly acquired fear memories.

Post-traumatic stress disorder (PTSD) is a severe anxiety disorder that affects women more than men. About 30% of patients suffering from PTSD develop the disorder by witnessing a traumatic event happen to someone else. However, as the focus has remained on those directly experiencing the traumatic...

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Main Authors: Shaghayegh Navabpour, Morgan B Patrick, Nour A Omar, Shannon E Kincaid, Yeeun Bae, Jennifer Abraham, Jacobi McGrew, Madeline Musaus, W Keith Ray, Richard F Helm, Timothy J Jarome
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2024-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0315564
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author Shaghayegh Navabpour
Morgan B Patrick
Nour A Omar
Shannon E Kincaid
Yeeun Bae
Jennifer Abraham
Jacobi McGrew
Madeline Musaus
W Keith Ray
Richard F Helm
Timothy J Jarome
author_facet Shaghayegh Navabpour
Morgan B Patrick
Nour A Omar
Shannon E Kincaid
Yeeun Bae
Jennifer Abraham
Jacobi McGrew
Madeline Musaus
W Keith Ray
Richard F Helm
Timothy J Jarome
author_sort Shaghayegh Navabpour
collection DOAJ
description Post-traumatic stress disorder (PTSD) is a severe anxiety disorder that affects women more than men. About 30% of patients suffering from PTSD develop the disorder by witnessing a traumatic event happen to someone else. However, as the focus has remained on those directly experiencing the traumatic event, whether indirectly acquired fear memories that underlie PTSD have the same molecular signature as those that are directly acquired remains unknown. Here, using a rodent indirect fear learning paradigm where one rat (observer) watches another rat (demonstrator) associate an auditory cue with foot shock, we found that fear can be indirectly acquired by both males and females regardless of the sex or novelty (familiarity) of the demonstrator animal. However, behaviorally, indirectly acquired fear responses resemble those of pseudoconditioning, a behavioral response that is thought to not represent learning. Despite this, using unbiased proteomics, we found that indirectly acquired fear memories have distinct protein degradation profiles in the amygdala and anterior cingulate cortex (ACC) relative to directly acquired fear memories and pseudoconditioning, which further differed significantly by sex. Additionally, Egr2 and c-fos expression in the retrosplenial cortex of observer animals resembled that of demonstrator rats but was significantly different than that of pseudoconditioned rats. Together, these findings reveal that indirectly acquired fear memories have sex-specific molecular signatures that differ from those of directly acquired fear memories or pseudoconditioning. These data have important implications for understanding the neurobiology of indirectly acquired fear memories that may underlie bystander PTSD.
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spelling doaj-art-215cd2f556b9460dbee31676002ae3782025-01-08T05:32:43ZengPublic Library of Science (PLoS)PLoS ONE1932-62032024-01-011912e031556410.1371/journal.pone.0315564Indirectly acquired fear memories have distinct, sex-specific molecular signatures from directly acquired fear memories.Shaghayegh NavabpourMorgan B PatrickNour A OmarShannon E KincaidYeeun BaeJennifer AbrahamJacobi McGrewMadeline MusausW Keith RayRichard F HelmTimothy J JaromePost-traumatic stress disorder (PTSD) is a severe anxiety disorder that affects women more than men. About 30% of patients suffering from PTSD develop the disorder by witnessing a traumatic event happen to someone else. However, as the focus has remained on those directly experiencing the traumatic event, whether indirectly acquired fear memories that underlie PTSD have the same molecular signature as those that are directly acquired remains unknown. Here, using a rodent indirect fear learning paradigm where one rat (observer) watches another rat (demonstrator) associate an auditory cue with foot shock, we found that fear can be indirectly acquired by both males and females regardless of the sex or novelty (familiarity) of the demonstrator animal. However, behaviorally, indirectly acquired fear responses resemble those of pseudoconditioning, a behavioral response that is thought to not represent learning. Despite this, using unbiased proteomics, we found that indirectly acquired fear memories have distinct protein degradation profiles in the amygdala and anterior cingulate cortex (ACC) relative to directly acquired fear memories and pseudoconditioning, which further differed significantly by sex. Additionally, Egr2 and c-fos expression in the retrosplenial cortex of observer animals resembled that of demonstrator rats but was significantly different than that of pseudoconditioned rats. Together, these findings reveal that indirectly acquired fear memories have sex-specific molecular signatures that differ from those of directly acquired fear memories or pseudoconditioning. These data have important implications for understanding the neurobiology of indirectly acquired fear memories that may underlie bystander PTSD.https://doi.org/10.1371/journal.pone.0315564
spellingShingle Shaghayegh Navabpour
Morgan B Patrick
Nour A Omar
Shannon E Kincaid
Yeeun Bae
Jennifer Abraham
Jacobi McGrew
Madeline Musaus
W Keith Ray
Richard F Helm
Timothy J Jarome
Indirectly acquired fear memories have distinct, sex-specific molecular signatures from directly acquired fear memories.
PLoS ONE
title Indirectly acquired fear memories have distinct, sex-specific molecular signatures from directly acquired fear memories.
title_full Indirectly acquired fear memories have distinct, sex-specific molecular signatures from directly acquired fear memories.
title_fullStr Indirectly acquired fear memories have distinct, sex-specific molecular signatures from directly acquired fear memories.
title_full_unstemmed Indirectly acquired fear memories have distinct, sex-specific molecular signatures from directly acquired fear memories.
title_short Indirectly acquired fear memories have distinct, sex-specific molecular signatures from directly acquired fear memories.
title_sort indirectly acquired fear memories have distinct sex specific molecular signatures from directly acquired fear memories
url https://doi.org/10.1371/journal.pone.0315564
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