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| Status |
Public on Jun 20, 2024 |
| Title |
Planar cell polarity proteins mediate ketamine-induced restoration of glutamatergic synapses in prefrontal cortical neurons in a mouse model for chronic stress |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
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.
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| Overall design |
C57BL/6J mice exposed to 35 µg/ml of CORT in the drinking water for 6 weeks. A control group received regular drinking water without CORT. After chronic CORT treatment, mice were treated with the fast-acting antidepressant Ket (10 mg/kg, i.p.). 24 h after Ket’s treatment, brains were harvested, and the prefrontal cortices were rapidly dissected and processed according to the manufacturer’s instructions.
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| Contributor(s) |
E. Freitas A, Feng B, Baker C, Galli S, Ban Y, Zou Y |
| Citation(s) |
38858386 |
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| Submission date |
Dec 15, 2021 |
| Last update date |
Jun 21, 2024 |
| Contact name |
Andiara Espindola de Freitas |
| E-mail(s) |
andiaraef@gmail.com
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| Phone |
858-281-3373
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| Organization name |
UC San Diego (UCSD)
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| Department |
Biological Sciences
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| Lab |
Zou Lab
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| Street address |
Gilman Drive
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| City |
San Diego |
| State/province |
California |
| ZIP/Postal code |
92121-2460 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (20)
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| Relations |
| BioProject |
PRJNA789535 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE191016_RAW.tar |
737.0 Mb |
(http)(custom) |
TAR (of MTX, TAR, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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