The Rap1 small GTPase is a critical mediator of the effects of stress on prefrontal cortical dysfunction.
Journal
Molecular psychiatry
ISSN: 1476-5578
Titre abrégé: Mol Psychiatry
Pays: England
ID NLM: 9607835
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
received:
02
10
2019
accepted:
30
06
2020
revised:
23
06
2020
pubmed:
12
7
2020
medline:
27
1
2022
entrez:
12
7
2020
Statut:
ppublish
Résumé
The neural molecular and biochemical response to stress is a distinct physiological process, and multiple lines of evidence indicate that the prefrontal cortex (PFC) is particularly sensitive to, and afflicted by, exposure to stress. Largely through this PFC dysfunction, stress has a characterized role in facilitating cognitive impairment, which is often dissociable from its effects on non-cognitive behaviors. The Rap1 small GTPase pathway has emerged as a commonly disrupted intracellular target in neuropsychiatric conditions, whether it be via alterations in Rap1 expression or through alterations in the expression of direct and specific upstream Rap1 activators and inhibitors. Here we demonstrate that escalating, intermittent stress increases Rap1 in mouse PFC synapses, results in cognitive impairments, and reduces the preponderance of mature dendritic spines in PFC neurons. Using viral-mediated gene transfer, we reveal that the hyper-induction of Rap1 in the PFC is sufficient to drive stress-relevant cognitive and synaptic phenotypes. These findings point to Rap1 as a critical mediator of stress-driven neuronal and behavioral pathology and highlight a previously unrecognized involvement for Rap1 in novelty-driven PFC engagement.
Identifiants
pubmed: 32651478
doi: 10.1038/s41380-020-0835-0
pii: 10.1038/s41380-020-0835-0
doi:
Substances chimiques
Rap1 protein, mouse
EC 3.6.5.2
rap1 GTP-Binding Proteins
EC 3.6.5.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3223-3239Informations de copyright
© 2020. The Author(s), under exclusive licence to Springer Nature Limited.
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