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The Rap1 small GTPase is a critical mediator of the effects of stress on prefrontal cortical dysfunction.

Authors :
Kermath BA
Vanderplow AM
Bjornson KJ
Seablom EN
Novak AM
Bernhardt CR
Cahill ME
Source :
Molecular psychiatry [Mol Psychiatry] 2021 Jul; Vol. 26 (7), pp. 3223-3239. Date of Electronic Publication: 2020 Jul 10.
Publication Year :
2021

Abstract

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.<br /> (© 2020. The Author(s), under exclusive licence to Springer Nature Limited.)

Details

Language :
English
ISSN :
1476-5578
Volume :
26
Issue :
7
Database :
MEDLINE
Journal :
Molecular psychiatry
Publication Type :
Academic Journal
Accession number :
32651478
Full Text :
https://doi.org/10.1038/s41380-020-0835-0