Acid sphingomyelinase – a regulator of canonical transient receptor potential channel 6 (TRPC6) activity
Recent investigations propose the acid sphingomyelinase (ASM)/ceramide system as a novel target for antidepressant action. ASM catalyzes the breakdown of the abundant membrane lipid sphingomyelin to the lipid messenger ceramide. This ASM‐induced lipid modification induces a local shift in membrane properties, which influences receptor clustering and downstream signaling. Canonical transient receptor potential channels 6 (TRPC6) are non‐selective cation channels located in the cell membrane that play an important role in dendritic growth, synaptic plasticity and cognition in the brain. They can be activated by hyperforin, an ingredient of the herbal remedy St. John’s wort for treatment of de…
Hyperforin Potentiates Antidepressant-Like Activity of Lanicemine in Mice
International audience; N-methyl-D-aspartate receptor (NMDAR) modulators induce rapid and sustained antidepressant like-activity in rodents through a molecular mechanism of action that involves the activation of Ca2+ dependent signaling pathways. Moreover, ketamine, a global NMDAR antagonist is a potent, novel, and atypical drug that has been successfully used to treat major depressive disorder (MDD). However, because ketamine evokes unwanted side effects, alternative strategies have been developed for the treatment of depression. The objective of the present study was to determine the antidepressant effects of either a single dose of hyperforin or lanicemine vs. their combined effects in m…
Antidepressant-like activity of hyperforin and changes in BDNF and zinc levels in mice exposed to chronic unpredictable mild stress.
Abstract Chronic unpredictable mild stress (CUMS) - a rodent model of depression mimics a variety of neurochemical and behavioral alterations similar to those seen in human depression. This study evaluated the antidepressant activity of hyperforin in the CUMS model using fluoxetine (FLX) as a reference drug. The antidepressant-like effects of hyperforin and FLX were evaluated in the tail suspension test (TST), forced swim test (FST), and splash test (SPT). CUMS induced an increase in immobility time in mice (pro-depressive effects) in the FST and TST. CUMS-induced changes were reversed by chronic treatment with hyperforin (2.5 and 5 mg/kg), as well as FLX (10 mg/kg). SPT results revealed a …