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Long term effects of peripubertal stress on excitatory and inhibitory circuits in the prefrontal cortex of male and female mice

The impact of stressful events is especially important during early life, because certain cortical regions, especially the prefrontal cortex (PFC), are still developing. Consequently, aversive experiences that occur during the peripubertal period can cause long-term alterations in neural connectivit...

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Autores principales: Bueno-Fernandez, Clara, Perez-Rando, Marta, Alcaide, Julia, Coviello, Simona, Sandi, Carmen, Castillo-Gómez, Esther, Nacher, Juan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045050/
https://www.ncbi.nlm.nih.gov/pubmed/33869684
http://dx.doi.org/10.1016/j.ynstr.2021.100322
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author Bueno-Fernandez, Clara
Perez-Rando, Marta
Alcaide, Julia
Coviello, Simona
Sandi, Carmen
Castillo-Gómez, Esther
Nacher, Juan
author_facet Bueno-Fernandez, Clara
Perez-Rando, Marta
Alcaide, Julia
Coviello, Simona
Sandi, Carmen
Castillo-Gómez, Esther
Nacher, Juan
author_sort Bueno-Fernandez, Clara
collection PubMed
description The impact of stressful events is especially important during early life, because certain cortical regions, especially the prefrontal cortex (PFC), are still developing. Consequently, aversive experiences that occur during the peripubertal period can cause long-term alterations in neural connectivity, physiology and related behaviors. Although sex influences the stress response and women are more likely to develop stress-related psychiatric disorders, knowledge about the effects of stress on females is still limited. In order to analyze the long-term effects of peripubertal stress (PPS) on the excitatory and inhibitory circuitry of the adult PFC, and whether these effects are sex-dependent, we applied an unpredictable chronic PPS protocol based on psychogenic stressors. Using two strains of transgenic mice with specific fluorescent cell reporters, we studied male and diestrus females to know how PPS affects the structure and connectivity of parvalbumin expressing (PV+) interneurons and pyramidal neurons. We also studied the expression of molecules related to excitatory and inhibitory neurotransmission, as well as alterations in the expression of plasticity-related molecules. The structure of pyramidal neurons was differentially affected by PPS in male and female mice: while the former had a decreased dendritic spine density, the latter displayed an increase in this parameter. PPS affected the density of puncta expressing excitatory and inhibitory synaptic markers exclusively in the female mPFC. Similarly, only in female mice we observed an increased complexity of the dendritic tree of PV+ neurons. Regarding the perisomatic innervation on pyramidal and PV + neurons by basket cells, we found a significant increase in the density of puncta in stressed animals, with interesting differences between the sexes and the type of basket cell analyzed. Finally, the PPS protocol also altered the total number of somata expressing the polysialylated form of the neural cell adhesion molecule (PSA-NCAM) when we analyzed both sexes together. These results highlight the strong programming effects of aversive experiences during early life for the establishment of cortical circuitry and the special impact of these stressful events on females.
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spelling pubmed-80450502021-04-16 Long term effects of peripubertal stress on excitatory and inhibitory circuits in the prefrontal cortex of male and female mice Bueno-Fernandez, Clara Perez-Rando, Marta Alcaide, Julia Coviello, Simona Sandi, Carmen Castillo-Gómez, Esther Nacher, Juan Neurobiol Stress Original Research Article The impact of stressful events is especially important during early life, because certain cortical regions, especially the prefrontal cortex (PFC), are still developing. Consequently, aversive experiences that occur during the peripubertal period can cause long-term alterations in neural connectivity, physiology and related behaviors. Although sex influences the stress response and women are more likely to develop stress-related psychiatric disorders, knowledge about the effects of stress on females is still limited. In order to analyze the long-term effects of peripubertal stress (PPS) on the excitatory and inhibitory circuitry of the adult PFC, and whether these effects are sex-dependent, we applied an unpredictable chronic PPS protocol based on psychogenic stressors. Using two strains of transgenic mice with specific fluorescent cell reporters, we studied male and diestrus females to know how PPS affects the structure and connectivity of parvalbumin expressing (PV+) interneurons and pyramidal neurons. We also studied the expression of molecules related to excitatory and inhibitory neurotransmission, as well as alterations in the expression of plasticity-related molecules. The structure of pyramidal neurons was differentially affected by PPS in male and female mice: while the former had a decreased dendritic spine density, the latter displayed an increase in this parameter. PPS affected the density of puncta expressing excitatory and inhibitory synaptic markers exclusively in the female mPFC. Similarly, only in female mice we observed an increased complexity of the dendritic tree of PV+ neurons. Regarding the perisomatic innervation on pyramidal and PV + neurons by basket cells, we found a significant increase in the density of puncta in stressed animals, with interesting differences between the sexes and the type of basket cell analyzed. Finally, the PPS protocol also altered the total number of somata expressing the polysialylated form of the neural cell adhesion molecule (PSA-NCAM) when we analyzed both sexes together. These results highlight the strong programming effects of aversive experiences during early life for the establishment of cortical circuitry and the special impact of these stressful events on females. Elsevier 2021-04-01 /pmc/articles/PMC8045050/ /pubmed/33869684 http://dx.doi.org/10.1016/j.ynstr.2021.100322 Text en © 2021 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Research Article
Bueno-Fernandez, Clara
Perez-Rando, Marta
Alcaide, Julia
Coviello, Simona
Sandi, Carmen
Castillo-Gómez, Esther
Nacher, Juan
Long term effects of peripubertal stress on excitatory and inhibitory circuits in the prefrontal cortex of male and female mice
title Long term effects of peripubertal stress on excitatory and inhibitory circuits in the prefrontal cortex of male and female mice
title_full Long term effects of peripubertal stress on excitatory and inhibitory circuits in the prefrontal cortex of male and female mice
title_fullStr Long term effects of peripubertal stress on excitatory and inhibitory circuits in the prefrontal cortex of male and female mice
title_full_unstemmed Long term effects of peripubertal stress on excitatory and inhibitory circuits in the prefrontal cortex of male and female mice
title_short Long term effects of peripubertal stress on excitatory and inhibitory circuits in the prefrontal cortex of male and female mice
title_sort long term effects of peripubertal stress on excitatory and inhibitory circuits in the prefrontal cortex of male and female mice
topic Original Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045050/
https://www.ncbi.nlm.nih.gov/pubmed/33869684
http://dx.doi.org/10.1016/j.ynstr.2021.100322
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