Ketamine induces apical extracellular matrix modifications in Caenorhabditis elegans

Area of Science:

• Neuroscience
• Developmental Biology
• Pharmacology

Background:

• Ketamine, an anesthetic, shows rapid antidepressant effects at subanesthetic doses.
• Ketamine induces extracellular matrix (ECM) alterations in rodents, potentially linked to its antidepressant action.
• Investigating ketamine's in vivo mechanisms requires further study, particularly in model organisms.

Purpose of the Study:

• To investigate ketamine-mediated alterations in the nematode Caenorhabditis elegans (C. elegans).
• To explore ketamine's effects on extracellular matrix (ECM) modifications and related developmental processes.
• To establish C. elegans as a model for studying ketamine's impact on ECM.

Main Methods:

• Utilized C. elegans as a model organism to study ketamine's effects.
• Observed ketamine-induced changes in apical extracellular matrix (aECM) in the vulva and cuticle.
• Analyzed neuronal migration, vulval development, and collagen expression in response to ketamine.
• Performed RNA sequencing to identify changes in collagen gene expression.

Main Results:

• Ketamine specifically induced apical extracellular matrix (aECM) modifications in the C. elegans vulva and cuticle.
• Ketamine treatment mimicked neuronal migration and vulval invagination defects seen in chondroitin mutants.
• Ketamine improved movement in roller mutants with collagen defects and upregulated 30% of cuticular collagens.
• Ketamine treatment altered aECM, neuronal migration, and collagen expression in C. elegans.

Conclusions:

• Ketamine induces specific apical extracellular matrix (aECM) modifications in C. elegans.
• C. elegans exhibits ketamine-induced developmental phenotypes related to ECM and collagen.
• C. elegans serves as a valuable model organism for investigating ketamine-mediated ECM alterations.