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Cited by 87Stress Responses and CortisolNeuroscience and Neuropharmacology ResearchMemory and Neural Mechanisms

Peripubertal stress-induced behavioral changes are associated with altered expression of genes involved in excitation and inhibition in the amygdala

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Tzanoulinou, S, Riccio, O, de Boer, M W, Sandi, C·2014·Translational Psychiatry
DOI 10.1038/tp.2014.54PMC PMC4119221
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Abstract

Early-life stress is a critical risk factor for developing psychopathological alterations later in life. This early adverse environment has been modeled in rats by exposure to stress during the peripubertal period-that is, corresponding to childhood and puberty-and has been shown to lead to increased emotionality, decreased sociability and pathological aggression. The amygdala, particularly its central nucleus (CeA), is hyperactivated in this model, consistent with evidence implicating this nucleus in the regulation of social and aggressive behaviors. Here, we investigated potential changes in the gene expression of molecular markers of excitatory and inhibitory neurotransmission in the CeA. We found that peripubertal stress led to an increase in the expression of mRNA encoding NR1 (the obligatory subunit of the N-methyl D-aspartate (NMDA) receptor) but to a reduction in the level of mRNA encoding glutamic acid decarboxylase 67 (GAD67), an enzyme that is critically involved in the activity-dependent synthesis of GABA, and to an increase in the vesicular glutamate transporter 1 (VGLUT1)/vesicular GABA transporter (VGAT) ratio in the CeA. These molecular alterations were present in addition to increased novelty reactivity, sociability deficits and increased aggression. Our results also showed that the full extent of the peripubertal protocol was required for the observed behavioral and neurobiological effects because exposure during only the childhood/prepubertal period (Juvenile Stress) or the male pubertal period (Puberty Stress) was insufficient to elicit the same effects. These findings highlight peripuberty as a period in which stress can lead to long-term programming of the genes involved in excitatory and inhibitory neurotransmission in the CeA.

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Authors
Tzanoulinou, S., Riccio, O., de Boer, M. W., & Sandi, C.
Affiliations
École Polytechnique Fédérale de Lausanne (CH)
Corresponding author
Sandi, C
ORCID
Venue
Translational Psychiatry
Publisher
Springer Science and Business Media LLC
Published
2014-07-08
Volume
4
Issue
7
Pages
e410-e410
ISSN
2158-3188 (ISSN-L)
DOI
10.1038/tp.2014.54
PMC
PMC4119221
OpenAlex
W2108999378
Cited by
87
References
9
Citations by year
2026: 6 · 2025: 4 · 2024: 4 · 2023: 10 · 2022: 2 · 2021: 8 · 2020: 6 · 2019: 9 · 2018: 11 · 2017: 8 · 2016: 10 · 2015: 7 · 2014: 2
FWCI
4.42
Type
journal article
Language
en
Open access
Licence
Locations
  • Translational Psychiatry (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
  • Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
Funders
  • National Science Foundation
  • Oak Foundation
  • École Polytechnique Fédérale de Lausanne
  • Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (135710)
Topics
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Keywords
early life stress, amygdala, central amygdala, excitatory and inhibitory neurotransmission, NMDA receptor NR1, GAD67, GABA synthesis, VGLUT1, vesicular GABA transporter, novelty reactivity, social dysfunction, aggression, puberty, developmental programming
MeSH terms
Age Factors, Animals, Behavior, Animal, Male, Random Allocation, Sexual Maturation, Stress, Psychological, Gene Expression, Rats, Wistar, Rats, Central Amygdaloid Nucleus

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