TRKB interaction with PSD95 is associated with latency of fluoxetine and 2R,6R-hydroxynorketamine.
Eur J Neurosci
; 57(8): 1215-1224, 2023 04.
Article
in En
| MEDLINE
| ID: mdl-36876503
ABSTRACT
Brain derived neurotrophic factor (BDNF) and its receptor tropomyosin kinase receptor B (TRKB) are key regulators of activity-dependent plasticity in the brain. TRKB is the target for both slow- and rapid-acting antidepressants and BDNF-TRKB system mediates the plasticity-inducing effects of antidepressants through their downstream targets. Particularly, the protein complexes that regulate the trafficking and synapse recruitment of TRKB receptors might be crucial in this process. In the present study, we investigated the interaction of TRKB with the postsynaptic density protein 95 (PSD95). We found that antidepressants increase the TRKBPSD95 interaction in adult mouse hippocampus. Fluoxetine, a slow-acting antidepressant, increases this interaction only after a long-term (7 days) treatment, while (2R,6R)-hydroxynorketamine (RHNK), an active metabolite of rapid-acting antidepressant ketamine, achieves this within a short treatment regimen (3 days). Moreover, the drug-induced changes of TRKBPSD95 interaction correlate with drug latency in behaviour, observed in mice subjected to an object location memory test (OLM). While silencing of PSD95 by viral delivery of shRNA in hippocampus abolished the RHNK-induced plasticity in mice in OLM, overexpression of PSD95 shortened the fluoxetine latency. In summary, changes in the TRKBPSD95 interaction contribute to differences observed in drug latency. This study sheds a light on a novel mechanism of action of different classes of antidepressants.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Fluoxetine
/
Brain-Derived Neurotrophic Factor
Type of study:
Risk_factors_studies
Limits:
Animals
Language:
En
Journal:
Eur J Neurosci
Journal subject:
NEUROLOGIA
Year:
2023
Document type:
Article
Affiliation country:
Finlandia