Stress-mediated dysregulation of the Rap1 small GTPase impairs hippocampal structure and function.

ABSTRACT: The effects of repeated stress on cognitive impairment are thought to be mediated, at least in part, by reductions in the stability of dendritic spines in brain regions critical for proper learning and memory, including the hippocampus. Small GTPases are particularly potent regulators of dendritic spine formation, stability, and morphology in hippocampal neurons. Through the use of small GTPase protein profiling in mice, we identify increased levels of synaptic Rap1 in the hippocampal CA3 region in response to escalating, intermittent stress. We then demonstrate that increased Rap1 in the CA3 is sufficient in and of itself to produce stress-relevant dendritic spine and cognitive phenotypes. Further, using super-resolution imaging, we investigate how the pattern of Rap1 trafficking to synap

SUBMITTER: Bjornson KJ 

PROVIDER: S-EPMC10470260 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature