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Schlagwörter:
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Zusammenfassung:
The aim of this study was to identify molecular pathways related to
antidepressant response. We administered paroxetine to the DBA/2J mice
for 28 days. Following the treatment, the mice were grouped into
responders or non-responders depending on the time they spent immobile
in the forced swim test. Hippocampal metabolomics and proteomics
analyses revealed that chronic paroxetine treatment affects
glutamate-related metabolite and protein levels differentially in the
two groups. We found significant differences in the expression of
N-methyl-D-aspartate receptor and neuronal nitric oxide synthase
proteins between the two groups, without any significant alterations in
the respective transcript levels. In addition, we found that chronic
paroxetine treatment altered the levels of proteins associated with the
ubiquitin-proteasome system (UPS). The soluble guanylate cyclase-beta 1,
proteasome subunit a type-2 and ubiquitination levels were also affected
in peripheral blood mononuclear cells from antidepressant responder and
non-responder patients suffering from major depressive disorder. We
submit that the glutamatergic system and UPS have a crucial role in the
antidepressant treatment response in both mice and humans.
