Unknown

Dataset Information

0

Importin ?5 Regulates Anxiety through MeCP2 and Sphingosine Kinase 1.


ABSTRACT: Importins mediate transport from synapse to soma and from cytoplasm to nucleus, suggesting that perturbation of importin-dependent pathways should have significant neuronal consequences. A behavioral screen on five importin ? knockout lines revealed that reduced expression of importin ?5 (KPNA1) in hippocampal neurons specifically decreases anxiety in mice. Re-expression of importin ?5 in ventral hippocampus of knockout animals increased anxiety behaviors to wild-type levels. Hippocampal neurons lacking importin ?5 reveal changes in presynaptic plasticity and modified expression of MeCP2-regulated genes, including sphingosine kinase 1 (Sphk1). Knockout of importin ?5, but not importin ?3 or ?4, reduces MeCP2 nuclear localization in hippocampal neurons. A Sphk1 blocker reverses anxiolysis in the importin ?5 knockout mouse, while pharmacological activation of sphingosine signaling has robust anxiolytic effects in wild-type animals. Thus, importin ?5 influences sphingosine-sensitive anxiety pathways by regulating MeCP2 nuclear import in hippocampal neurons.

SUBMITTER: Panayotis N 

PROVIDER: S-EPMC6302549 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC5955436 | biostudies-literature
| S-EPMC3918136 | biostudies-literature
| S-EPMC9115769 | biostudies-literature
| S-EPMC7305159 | biostudies-literature
| S-EPMC8206894 | biostudies-literature
| S-EPMC7806667 | biostudies-literature
| S-EPMC9709229 | biostudies-literature
2021-06-22 | GSE174304 | GEO
| S-EPMC3962613 | biostudies-literature
| S-EPMC2651020 | biostudies-literature