Data Entry: Please note that the research database will be replaced by UNIverse by the end of October 2023. Please enter your data into the system https://universe-intern.unibas.ch. Thanks

Login for users with Unibas email account...

Login for registered users without Unibas email account...

 
(-)- Gossypol Inhibition of Musashi-Mediated Forgetting Improves Memory and Age-Dependent Memory Decline in Caenorhabditis elegans
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
 
ID 4652286
Author(s) Mastrandreas, Pavlina; Arnold, Andreas; Boglari, Csaba; de Quervain, Dominique J.-F.; Stetak, Attila; Papassotiropoulos, Andreas
Author(s) at UniBasel Papassotiropoulos, Andreas
Year 2022
Title (-)- Gossypol Inhibition of Musashi-Mediated Forgetting Improves Memory and Age-Dependent Memory Decline in Caenorhabditis elegans
Journal Molecular neurobiology
Volume 60
Number 2
Pages / Article-Number 820-835
Keywords (-)- Gossypol; Ageing; C. elegans; Forgetting; Musashi
Mesh terms Animals; Humans; Aged; Caenorhabditis elegans, metabolism; Gossypol, metabolism; Neurons, metabolism; Stem Cells, metabolism; Memory Disorders, drug therapy; Nerve Tissue Proteins, metabolism; RNA-Binding Proteins, metabolism
Abstract Musashi RNA-binding proteins (MSIs) retain a pivotal role in stem cell maintenance, tumorigenesis, and nervous system development. Recently, we showed in C. elegans that Musashi (MSI-1) actively promotes forgetting upon associative learning via a 3'UTR-dependent translational expression of the Arp2/3 actin branching complex. Here, we investigated the evolutionary conserved role of MSI proteins and the effect of their pharmacological inhibition on memory. Expression of human Musashi 1 (MSI1) and Musashi 2 (MSI2) under the endogenous Musashi promoter fully rescued the phenotype of msi-1(lf) worms. Furthermore, pharmacological inhibition of human MSI1 and MSI2 activity using (-)- gossypol resulted in improved memory retention, without causing locomotor, chemotactic, or learning deficits. No drug effect was observed in msi-1(lf) treated worms. Using Western blotting and confocal microscopy, we found no changes in MSI-1 protein abundance following (-)- gossypol treatment, suggesting that Musashi gene expression remains unaltered and that the compound exerts its inhibitory effect post-translationally. Additionally, (-)- gossypol suppressed the previously seen rescue of the msi-1(lf) phenotype in worms expressing human MSI1 specifically in the AVA neuron, indicating that (-)- gossypol can regulate the Musashi pathway in a memory-related neuronal circuit in worms. Finally, treating aged worms with (-)- gossypol reversed physiological age-dependent memory decline. Taken together, our findings indicate that pharmacological inhibition of Musashi might represent a promising approach for memory modulation.
Publisher Springer
ISSN/ISBN 0893-7648 ; 1559-1182
edoc-URL https://edoc.unibas.ch/90874/
Full Text on edoc Restricted
Digital Object Identifier DOI 10.1007/s12035-022-03116-7
PubMed ID http://www.ncbi.nlm.nih.gov/pubmed/36378468
ISI-Number WOS:000884156600003
Document type (ISI) Journal Article
 
   

MCSS v5.8 PRO. 0.331 sec, queries - 0.000 sec ©Universität Basel  |  Impressum   |    
29/03/2024