Molecular signatures of astrocytes and microglia maladaptive responses to acute stress are rescued by a single administration of ketamine in a rodent model of PTSD.
Journal
Translational psychiatry
ISSN: 2158-3188
Titre abrégé: Transl Psychiatry
Pays: United States
ID NLM: 101562664
Informations de publication
Date de publication:
25 May 2024
25 May 2024
Historique:
received:
27
11
2023
accepted:
13
05
2024
revised:
09
05
2024
medline:
26
5
2024
pubmed:
26
5
2024
entrez:
25
5
2024
Statut:
epublish
Résumé
Stress affects the brain and alters its neuroarchitecture and function; these changes can be severe and lead to psychiatric disorders. Recent evidence suggests that astrocytes and microglia play an essential role in the stress response by contributing to the maintenance of cerebral homeostasis. These cells respond rapidly to all stimuli that reach the brain, including stressors. Here, we used a recently validated rodent model of post-traumatic stress disorder in which rats can be categorized as resilient or vulnerable after acute inescapable footshock stress. We then investigated the functional, molecular, and morphological determinants of stress resilience and vulnerability in the prefrontal cortex, focusing on glial and neuronal cells. In addition, we examined the effects of a single subanesthetic dose of ketamine, a fast-acting antidepressant recently approved for the treatment of resistant depression and proposed for other stress-related psychiatric disorders. The present results suggest a prompt glial cell response and activation of the NF-κB pathway after acute stress, leading to an increase in specific cytokines such as IL-18 and TNF-α. This response persists in vulnerable individuals and is accompanied by a significant change in the levels of critical glial proteins such as S100B, CD11b, and CX43, brain trophic factors such as BDNF and FGF2, and proteins related to dendritic arborization and synaptic architecture such as MAP2 and PSD95. Administration of ketamine 24 h after the acute stress event rescued many of the changes observed in vulnerable rats, possibly contributing to support brain homeostasis. Overall, our results suggest that pivotal events, including reactive astrogliosis, changes in brain trophic factors, and neuronal damage are critical determinants of vulnerability to acute traumatic stress and confirm the therapeutic effect of acute ketamine against the development of stress-related psychiatric disorders.
Identifiants
pubmed: 38796504
doi: 10.1038/s41398-024-02928-6
pii: 10.1038/s41398-024-02928-6
doi:
Substances chimiques
Ketamine
690G0D6V8H
NF-kappa B
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
209Subventions
Organisme : Sapienza Università di Roma (Sapienza University of Rome)
ID : RG12218168987A63
Organisme : Sapienza Università di Roma (Sapienza University of Rome)
ID : prot. AR22117A5DC9F3F2
Organisme : Sapienza Università di Roma (Sapienza University of Rome)
ID : prot. AR22117A7347A4F9
Organisme : Sapienza Università di Roma (Sapienza University of Rome)
ID : prot. AR22218168996B83
Organisme : Ministero dell'Istruzione, dell'Università e della Ricerca (Ministry of Education, University and Research)
ID : PRIN 2015HRE757
Organisme : Ministero dell'Istruzione, dell'Università e della Ricerca (Ministry of Education, University and Research)
ID : PRIN 2015HRE757
Organisme : Ministero dell'Istruzione, dell'Università e della Ricerca (Ministry of Education, University and Research)
ID : PRIN 2015HRE757
Organisme : Università degli Studi di Genova (University of Genoa)
ID : PRA-2013, Prot. 9563, CUPD34G13000170005
Informations de copyright
© 2024. The Author(s).
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