Project description:We performed single cell transcriptomics analyses in medial prefrontal cortical (mPFC) and basolateral amygdala (BLA). Ketamine induced changes in inflammatory pathways reversing corticosterone effects. Cell-cell communication analyses predicted that planar-cell-polarity (PCP) signaling is decreased after corticosterone but increased following ketamine administration in excitatory neurons. Single cell transcriptomics analyses in dorsolateral prefrontal cortical (dl-PFC) neurons of depressed patients also showed decreased PCP signaling in excitatory neurons. Using chemogenetics, we found that the BLA-projecting infra limbic prefrontal cortex (IL PFC) neurons regulate immobility time in the tail suspension test and food consumption. Using RNAScope, we found, in the excitatory neurons in mPFC, Celsrs and Prickle2 were reduced by corticosterone but increased by ketamine. Using CRISPR-Cas9, we conditionally knocked out Celsrs and Prickle2 in the BLA-projecting IL-PFC neurons and found that ketamine-induced synapse restoration and behavioral remission were abolished. Ketamine affects gene expression and PCP proteins underly long-lasting effects of low-dose ketamine.

2024-06-20 | GSE191016 | GEO

Prickle is phosphorylated by Nemo and targeted for degradation to maintain Prickle/Spiny-legs isoform balance during planar cell polarity establishment.

Project description: Not available

| S-EPMC5967807 | biostudies-literature

A Dual Function for Prickle in Regulating Frizzled Stability during Feedback-Dependent Amplification of Planar Polarity.

Project description: Not available

| S-EPMC5628951 | biostudies-literature

Prickle and Strabismus form a functional complex to generate a correct axis during planar cell polarity signaling.

Project description: Not available

| S-EPMC202366 | biostudies-literature

Clustering and negative feedback by endocytosis in planar cell polarity signaling is modulated by ubiquitinylation of prickle.

Project description: Not available