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Heterotypic stressors unmask behavioral influences of PMAT deficiency in mice

Certain life stressors having enduring physiological and behavioral consequences, in part by eliciting dramatic signaling shifts in monoamine neurotransmitters. High monoamine levels can overwhelm selective transporters like the serotonin transporter. This is when polyspecific transporters like plas...

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Autores principales: Weber, Brady L, Nicodemus, Marissa M, Hite, Allianna K, Spalding, Isabella R, Beaver, Jasmin N, Scrimshaw, Lauren R, Kassis, Sarah K, Reichert, Julie M, Ford, Matthew T, Russell, Cameron N, Hallal, Elayna M, Gilman, T Lee
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10491137/
https://www.ncbi.nlm.nih.gov/pubmed/37693400
http://dx.doi.org/10.1101/2023.08.30.555632
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author Weber, Brady L
Nicodemus, Marissa M
Hite, Allianna K
Spalding, Isabella R
Beaver, Jasmin N
Scrimshaw, Lauren R
Kassis, Sarah K
Reichert, Julie M
Ford, Matthew T
Russell, Cameron N
Hallal, Elayna M
Gilman, T Lee
author_facet Weber, Brady L
Nicodemus, Marissa M
Hite, Allianna K
Spalding, Isabella R
Beaver, Jasmin N
Scrimshaw, Lauren R
Kassis, Sarah K
Reichert, Julie M
Ford, Matthew T
Russell, Cameron N
Hallal, Elayna M
Gilman, T Lee
author_sort Weber, Brady L
collection PubMed
description Certain life stressors having enduring physiological and behavioral consequences, in part by eliciting dramatic signaling shifts in monoamine neurotransmitters. High monoamine levels can overwhelm selective transporters like the serotonin transporter. This is when polyspecific transporters like plasma membrane monoamine transporter (PMAT, Slc29a4) are hypothesized to contribute most to monoaminergic signaling regulation. Here, we employed two distinct counterbalanced stressors – fear conditioning, and swim stress – in mice to systematically determine how reductions in PMAT function affect heterotypic stressor responsivity. We hypothesized male heterozygotes would exhibit augmented stressor responses relative to female heterozygotes. Decreased PMAT function enhanced context fear expression, an effect unexpectedly obscured by a sham stress condition. Impaired cued fear extinction retention and enhanced context fear expression in males were conversely unmasked by a sham swim condition. Abrogated corticosterone levels in male heterozygotes that underwent swim stress after context fear conditioning did not map on to any measured behaviors. In sum, male heterozygous mouse fear behaviors proved malleable in response to preceding stressor or sham stress exposure. Combined, these data indicate reduced male PMAT function elicits a form of stress-responsive plasticity. Future studies should assess how PMAT is differentially affected across sexes and identify downstream consequences of the stress-shifted corticosterone dynamics.
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spelling pubmed-104911372023-11-20 Heterotypic stressors unmask behavioral influences of PMAT deficiency in mice Weber, Brady L Nicodemus, Marissa M Hite, Allianna K Spalding, Isabella R Beaver, Jasmin N Scrimshaw, Lauren R Kassis, Sarah K Reichert, Julie M Ford, Matthew T Russell, Cameron N Hallal, Elayna M Gilman, T Lee bioRxiv Article Certain life stressors having enduring physiological and behavioral consequences, in part by eliciting dramatic signaling shifts in monoamine neurotransmitters. High monoamine levels can overwhelm selective transporters like the serotonin transporter. This is when polyspecific transporters like plasma membrane monoamine transporter (PMAT, Slc29a4) are hypothesized to contribute most to monoaminergic signaling regulation. Here, we employed two distinct counterbalanced stressors – fear conditioning, and swim stress – in mice to systematically determine how reductions in PMAT function affect heterotypic stressor responsivity. We hypothesized male heterozygotes would exhibit augmented stressor responses relative to female heterozygotes. Decreased PMAT function enhanced context fear expression, an effect unexpectedly obscured by a sham stress condition. Impaired cued fear extinction retention and enhanced context fear expression in males were conversely unmasked by a sham swim condition. Abrogated corticosterone levels in male heterozygotes that underwent swim stress after context fear conditioning did not map on to any measured behaviors. In sum, male heterozygous mouse fear behaviors proved malleable in response to preceding stressor or sham stress exposure. Combined, these data indicate reduced male PMAT function elicits a form of stress-responsive plasticity. Future studies should assess how PMAT is differentially affected across sexes and identify downstream consequences of the stress-shifted corticosterone dynamics. Cold Spring Harbor Laboratory 2023-11-13 /pmc/articles/PMC10491137/ /pubmed/37693400 http://dx.doi.org/10.1101/2023.08.30.555632 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
spellingShingle Article
Weber, Brady L
Nicodemus, Marissa M
Hite, Allianna K
Spalding, Isabella R
Beaver, Jasmin N
Scrimshaw, Lauren R
Kassis, Sarah K
Reichert, Julie M
Ford, Matthew T
Russell, Cameron N
Hallal, Elayna M
Gilman, T Lee
Heterotypic stressors unmask behavioral influences of PMAT deficiency in mice
title Heterotypic stressors unmask behavioral influences of PMAT deficiency in mice
title_full Heterotypic stressors unmask behavioral influences of PMAT deficiency in mice
title_fullStr Heterotypic stressors unmask behavioral influences of PMAT deficiency in mice
title_full_unstemmed Heterotypic stressors unmask behavioral influences of PMAT deficiency in mice
title_short Heterotypic stressors unmask behavioral influences of PMAT deficiency in mice
title_sort heterotypic stressors unmask behavioral influences of pmat deficiency in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10491137/
https://www.ncbi.nlm.nih.gov/pubmed/37693400
http://dx.doi.org/10.1101/2023.08.30.555632
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